{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:05:25Z","timestamp":1790244325167,"version":"4.1.0"},"reference-count":210,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Encoding genetic information involves both structure and sequence. Non-protein-coding (NCR) RNAs modulate host immune responses by guiding and assembling stress-specific protein effectors, with flipons enabling dynamic transitions between states. Small NCRs transcribed by both RNA Polymerases 2 and 3 normally modulate these pathways. The miRNAs, tRNA fragments, mitrons, piRNAs, and endo-small-interfering RNA products target the guide effector complexes to their targets. These NCRs filter the subset of RNAs that are translated, a process modulated by other NCRs that fine-tune RNA stability, localization, and kinetics through the modifications they direct. When these RNAs, or their targets, are dysregulated, host interferon responses are activated through the accumulation of uncapped triphosphorylated RNAs, dsRNAs, or flipon-encoded Z-RNAs. These responses are initially suppressed to avoid attacks on self-RNAs, but above a threshold, highly immunogenic pathways are unleashed. These same responses resist viral and other infections without pathogen-specific effectors or prior exposure. They also eliminate dysfunctional cells. These universal responses, when unresolved, contribute to a range of pathologies, increasing cancer, inflammatory diseases, and senescence. The review focuses on recent findings showing how these integrated host responses are driven by, and exploit, the retrotransposon invasion of animal genomes.<\/jats:p>","DOI":"10.3390\/ijms27198526","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:07:54Z","timestamp":1790240874000},"page":"8526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Flipons, Noncoding Transcripts and Retroelements: A Universal Host Defense"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-1572","authenticated-orcid":false,"given":"Alan","family":"Herbert","sequence":"first","affiliation":[{"name":"Discovery, InsideOutBio, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.tig.2019.09.007","article-title":"A Genetic Instruction Code Based on DNA Conformation","volume":"35","author":"Herbert","year":"2019","journal-title":"Trends Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11846","DOI":"10.1016\/S0021-9258(19)49776-7","article-title":"Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes","volume":"267","author":"Schroth","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1093\/nar\/gki609","article-title":"Prevalence of quadruplexes in the human genome","volume":"33","author":"Huppert","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"D383","DOI":"10.1093\/nar\/gkq1170","article-title":"Non-B DB: A database of predicted non-B DNA-forming motifs in mammalian genomes","volume":"39","author":"Cer","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nchem.1548","article-title":"Quantitative visualization of DNA G-quadruplex structures in human cells","volume":"5","author":"Biffi","year":"2013","journal-title":"Nat. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1093\/nar\/gky1305","article-title":"Isolation and genome-wide characterization of cellular DNA:RNA triplex structures","volume":"47","author":"Kuo","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s42003-018-0237-x","article-title":"Z-DNA and Z-RNA in human disease","volume":"2","author":"Herbert","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19134","DOI":"10.1038\/s41598-020-76203-1","article-title":"Deep learning approach for predicting functional Z-DNA regions using omics data","volume":"10","author":"Beknazarov","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/nar\/gkaa1269","article-title":"Non-B DNA: A major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome","volume":"49","author":"Guiblet","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100111","DOI":"10.1016\/j.xgen.2022.100111","article-title":"High-throughput characterization of the role of non-B DNA motifs on promoter function","volume":"2","author":"Victorino","year":"2022","journal-title":"Cell Genom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e202301962","DOI":"10.26508\/lsa.202301962","article-title":"Z-flipon variants reveal the many roles of Z-DNA and Z-RNA in health and disease","volume":"6","author":"Umerenkov","year":"2023","journal-title":"Life Sci. Alliance"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23119","DOI":"10.1038\/s41598-025-07579-1","article-title":"Deep learning deciphers the related role of master regulators and G-quadruplexes in tissue specification","volume":"15","author":"Bashkatov","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"gkaf1007","DOI":"10.1093\/nar\/gkaf1007","article-title":"GQ-DNABERT reveals GQ proximal enhancer-promoter interactions associated with tissue-specific transcription","volume":"53","author":"Konovalov","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1073\/pnas.90.8.3339","article-title":"Z-DNA binding protein from chicken blood nuclei","volume":"90","author":"Herbert","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7550","DOI":"10.1073\/pnas.92.16.7550","article-title":"Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA","volume":"92","author":"Herbert","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.1073\/pnas.94.16.8421","article-title":"A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase","volume":"94","author":"Herbert","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20240635","DOI":"10.1098\/rsbl.2024.0635","article-title":"Flipons and the origin of the genetic code","volume":"21","author":"Herbert","year":"2025","journal-title":"Biol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41467-021-21039-0","article-title":"Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions","volume":"12","author":"Nichols","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Herbert, A. (2024). Neurodegenerative diseases reflect the reciprocal roles played by retroelements in regulating memory and immunity. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1445540"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1101\/gr.5826307","article-title":"The evolutionary history of human DNA transposons: Evidence for intense activity in the primate lineage","volume":"17","author":"Pace","year":"2007","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1101\/gr.277722.123","article-title":"Genetic features and genomic targets of human KRAB-zinc finger proteins","volume":"33","author":"Thorball","year":"2023","journal-title":"Genome Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrg2640","article-title":"The impact of retrotransposons on human genome evolution","volume":"10","author":"Cordaux","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrg.2016.139","article-title":"Regulatory activities of transposable elements: From conflicts to benefits","volume":"18","author":"Chuong","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"eads8412","DOI":"10.1126\/science.ads8412","article-title":"Structural mechanism of LINE-1 target-primed reverse transcription","volume":"388","author":"Ghanim","year":"2025","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.cell.2010.05.021","article-title":"LINE-1 retrotransposition activity in human genomes","volume":"141","author":"Beck","year":"2010","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1101\/gr.248823.119","article-title":"Discovering human transcription factor physical interactions with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays","volume":"29","author":"Shrestha","year":"2019","journal-title":"Genome Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7594","DOI":"10.1038\/s41467-024-51921-6","article-title":"Regulatory transposable elements in the encyclopedia of DNA elements","volume":"15","author":"Du","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1042\/BST20160062","article-title":"Transcription by RNA polymerase III: Insights into mechanism and regulation","volume":"44","author":"Turowski","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nature25441","article-title":"Structural basis of RNA polymerase III transcription initiation","volume":"553","author":"Ramsay","year":"2018","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.molcel.2019.10.020","article-title":"TFIIIC Binding to Alu Elements Controls Gene Expression via Chromatin Looping and Histone Acetylation","volume":"77","author":"Ferrari","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e27639","DOI":"10.4161\/trns.27369","article-title":"Comparative overview of RNA polymerase II and III transcription cycles, with focus on RNA polymerase III termination and reinitiation","volume":"5","author":"Arimbasseri","year":"2014","journal-title":"Transcription"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.it.2023.04.002","article-title":"The RNA polymerase III-RIG-I axis in antiviral immunity and inflammation","volume":"44","author":"Naesens","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eabm9875","DOI":"10.1126\/sciadv.abm9875","article-title":"An integrated model for termination of RNA polymerase III transcription","volume":"8","author":"Xie","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kawaji, H., Nakamura, M., Takahashi, Y., Sandelin, A., Katayama, S., Fukuda, S., Daub, C.O., Kai, C., Kawai, J., and Yasuda, J. (2008). Hidden layers of human small RNAs. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-157"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6787","DOI":"10.1093\/nar\/gks307","article-title":"Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs","volume":"40","author":"Li","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-genet-022620-101840","article-title":"Noncanonical Roles of tRNAs: TRNA Fragments and Beyond","volume":"54","author":"Su","year":"2020","journal-title":"Annu. Rev. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108153","DOI":"10.1016\/j.phrs.2026.108153","article-title":"tRNA-derived small RNAs in pulmonary diseases: Regulatory functions and clinical prospects","volume":"226","author":"Wang","year":"2026","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cell.2017.06.013","article-title":"LTR-Retrotransposon Control by tRNA-Derived Small RNAs","volume":"170","author":"Schorn","year":"2017","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/cr.2017.109","article-title":"TsRNAs: New players in mammalian retrotransposon control","volume":"27","author":"Zhang","year":"2017","journal-title":"Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1261\/rna.066126.118","article-title":"TRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner","volume":"24","author":"Kuscu","year":"2018","journal-title":"RNA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41580-019-0136-0","article-title":"The roles of structural dynamics in the cellular functions of RNAs","volume":"20","author":"Ganser","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/21541264.2022.2047583","article-title":"Emerging insights into the function and structure of the Integrator complex","volume":"12","author":"Pfleiderer","year":"2021","journal-title":"Transcription"},{"key":"ref_43","first-page":"1625","article-title":"An old friend with a new face: TRNA-derived small RNAs with big regulatory potential in cancer biology","volume":"128","author":"Gullerova","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1139\/gen-2023-0136","article-title":"Fragments derived from non-coding RNAs: How complex is genome regulation?","volume":"67","year":"2024","journal-title":"Genome"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nsmb.2879","article-title":"The evolutionary journey of Argonaute proteins","volume":"21","author":"Swarts","year":"2014","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41586-026-10640-2","article-title":"Structural basis for chaperone-guided assembly of RNA-induced silencing complex","volume":"655","author":"Lee","year":"2026","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrm.2017.20","article-title":"The HSP90 chaperone machinery","volume":"18","author":"Schopf","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2216330120","DOI":"10.1073\/pnas.2216330120","article-title":"Nicked tRNAs are stable reservoirs of tRNA halves in cells and biofluids","volume":"120","author":"Costa","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kumar, P., Anaya, J., Mudunuri, S.B., and Dutta, A. (2014). Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. BMC Biol., 12.","DOI":"10.1186\/s12915-014-0078-0"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6618","DOI":"10.1093\/nar\/gkac519","article-title":"Anatomy of four human Argonaute proteins","volume":"50","author":"Nakanishi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Choi, E.J., Ren, J., Zhang, K., Wu, W., Lee, Y.S., Lee, I., and Bao, X. (2020). The Importance of AGO 1 and 4 in Post-Transcriptional Gene Regulatory Function of tRF5-GluCTC, an Respiratory Syncytial Virus-Induced tRNA-Derived RNA Fragment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228766"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1534\/genetics.107.072553","article-title":"Origin and evolution of human microRNAs from transposable elements","volume":"176","author":"Piriyapongsa","year":"2007","journal-title":"Genetics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6568","DOI":"10.1093\/nar\/gkt361","article-title":"Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing","volume":"41","author":"Lee","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rogato, A., Richard, H., Sarazin, A., Voss, B., Cheminant Navarro, S., Champeimont, R., Navarro, L., Carbone, A., Hess, W.R., and Falciatore, A. (2014). The diversity of small non-coding RNAs in the diatom Phaeodactylum tricornutum. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-698"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","article-title":"Metazoan MicroRNAs","volume":"173","author":"Bartel","year":"2018","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1073\/pnas.0710869105","article-title":"In vitro reconstitution of the human RISC-loading complex","volume":"105","author":"MacRae","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.celrep.2014.09.039","article-title":"Deletion of human tarbp2 reveals cellular microRNA targets and cell-cycle function of TRBP","volume":"9","author":"Kim","year":"2014","journal-title":"Cell Rep."},{"key":"ref_59","first-page":"1539","article-title":"From activator to suppressor: PACT is joining the company of PKR negative regulators","volume":"31","author":"Acosta","year":"2025","journal-title":"RNA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.molcel.2016.05.026","article-title":"The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway","volume":"63","author":"Hasler","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1261\/rna.068189.118","article-title":"TRNA deamination by ADAT requires substrate-specific recognition mechanisms and can be inhibited by tRFs","volume":"25","author":"Camacho","year":"2019","journal-title":"RNA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13228","DOI":"10.1096\/fj.201900382RR","article-title":"A novel 3\u2032-tRNA(Glu)-derived fragment acts as a tumor suppressor in breast cancer by targeting nucleolin","volume":"33","author":"Falconi","year":"2019","journal-title":"FASEB J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41419-022-04930-6","article-title":"A novel 3\u2032tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer","volume":"13","author":"Cui","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e202302488","DOI":"10.26508\/lsa.202302488","article-title":"Structural basis of translation inhibition by a valine tRNA-derived fragment","volume":"7","author":"Wu","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ando, D., Rashad, S., Begley, T.J., Endo, H., Aoki, M., Dedon, P.C., and Niizuma, K. (2025). Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020706"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"16930","DOI":"10.1074\/jbc.RA119.009272","article-title":"Angiogenin generates specific stress-induced tRNA halves and is not involved in tRF-3-mediated gene silencing","volume":"294","author":"Su","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"18201","DOI":"10.1073\/pnas.1407361111","article-title":"G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments","volume":"111","author":"Ivanov","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s41467-017-01278-w","article-title":"Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs","volume":"8","author":"Lyons","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9081","DOI":"10.1093\/nar\/gky495","article-title":"Dimerization confers increased stability to nucleases in 5\u2032 halves from glycine and glutamic acid tRNAs","volume":"46","author":"Tosar","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/s13046-021-02024-3","article-title":"A 5\u2032-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer","volume":"40","author":"Han","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9273","DOI":"10.1038\/s41467-024-53624-4","article-title":"5\u2032-tRNAGly(GCC) halves generated by IRE1\u03b1 are linked to the ER stress response","volume":"15","author":"Jin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.cmet.2024.02.011","article-title":"Aging-induced tRNA(Glu)-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization","volume":"36","author":"Li","year":"2024","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"115128","DOI":"10.1016\/j.expneurol.2024.115128","article-title":"Effects of ALS-associated 5\u2032tiRNA(Gly-GCC) on the transcriptomic and proteomic profile of primary neurons in vitro","volume":"385","author":"Jirstrom","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1093\/nar\/gkq1216","article-title":"Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells","volume":"39","author":"Detzer","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.molcel.2011.04.015","article-title":"Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm","volume":"42","author":"Leung","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"42708","DOI":"10.1074\/jbc.M112.371799","article-title":"Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress","volume":"287","author":"Saikia","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5796","DOI":"10.1038\/s41467-023-41554-6","article-title":"Discovery of the major 15-30 nt mammalian small RNAs, their biogenesis and function","volume":"14","author":"Lai","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature05983","article-title":"Intronic microRNA precursors that bypass Drosha processing","volume":"448","author":"Ruby","year":"2007","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/nature05939","article-title":"A microRNA component of the p53 tumour suppressor network","volume":"447","author":"He","year":"2007","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cmet.2009.08.015","article-title":"MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1\/2","volume":"10","author":"Chan","year":"2009","journal-title":"Cell Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.molcel.2010.09.027","article-title":"MicroRNA functions in stress responses","volume":"40","author":"Leung","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00018-017-2591-0","article-title":"Stress-induced changes in miRNA biogenesis and functioning","volume":"75","author":"Olejniczak","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"108276","DOI":"10.1016\/j.jbc.2025.108276","article-title":"RNA G-quadruplexes regulate mammalian mirtron biogenesis","volume":"301","author":"Salim","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nrg798","article-title":"Alu repeats and human genomic diversity","volume":"3","author":"Batzer","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1038\/ncomms7569","article-title":"SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation","volume":"6","author":"Varshney","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1093\/nar\/gku1361","article-title":"Identification of RNA polymerase III-transcribed Alu loci by computational screening of RNA-Seq data","volume":"43","author":"Conti","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"200222","DOI":"10.1098\/rsos.200222","article-title":"ALU non-B-DNA conformations, flipons, binary codes and evolution","volume":"7","author":"Herbert","year":"2020","journal-title":"R. Soc. Open Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Herbert, A., Cherednichenko, O., Lybrand, T.P., Egli, M., and Poptsova, M. (2025). Z\u03b1 and Z\u03b2 Localize ADAR1 to Flipons That Modulate Innate Immunity, Alternative Splicing, and Nonsynonymous RNA Editing. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062422"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"gkag419","DOI":"10.1093\/nar\/gkag419","article-title":"Z\u03b1 and Z\u03b2 domains of ADAR1 and ZBP1 bind G-quadruplexes with nanomolar affinities, establishing Z\u03b2 as a G-quadruplex-specific domain","volume":"54","author":"Kroft","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/nar\/23.10.1758","article-title":"Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts","volume":"23","author":"Liu","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1006\/jmbi.1995.0239","article-title":"Activation of expression of multiple subfamilies of human Alu elements by adenovirus type 5 and herpes simplex virus type 1","volume":"248","author":"Panning","year":"1995","journal-title":"J. Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9481","DOI":"10.1093\/nar\/gkae615","article-title":"Adenovirus small E1A directs activation of Alu transcription at YAP\/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler","volume":"52","author":"Cantarella","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"R117","DOI":"10.1186\/gb-2011-12-11-r117","article-title":"Heat shock factor binding in Alu repeats expands its involvement in stress through an antisense mechanism","volume":"12","author":"Pandey","year":"2011","journal-title":"Genome Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"102951","DOI":"10.1016\/j.isci.2021.102951","article-title":"Structures of heat shock factor trimers bound to DNA","volume":"24","author":"Feng","year":"2021","journal-title":"iScience"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.molcel.2007.12.013","article-title":"Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock","volume":"29","author":"Mariner","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5569","DOI":"10.1073\/pnas.0810738106","article-title":"B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes","volume":"106","author":"Yakovchuk","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41594-024-01448-7","article-title":"Mechanism of mammalian transcriptional repression by noncoding RNA","volume":"32","author":"Tluckova","year":"2025","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/nature749","article-title":"Hsp90 as a capacitor of phenotypic variation","volume":"417","author":"Queitsch","year":"2002","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1101\/gr.249789.119","article-title":"Genome-wide analysis of polymerase III-transcribed Alu elements suggests cell-type-specific enhancer function","volume":"29","author":"Zhang","year":"2019","journal-title":"Genome Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/nsmb.1801","article-title":"Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors","volume":"17","author":"Oler","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1042\/BST20230770","article-title":"The choreography of chromatin in RNA polymerase III regulation","volume":"52","author":"Gerber","year":"2024","journal-title":"Biochem. Soc. Trans."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Laperriere, D., Wang, T.T., White, J.H., and Mader, S. (2007). Widespread Alu repeat-driven expansion of consensus DR2 retinoic acid response elements during primate evolution. BMC Genom., 8.","DOI":"10.1186\/1471-2164-8-23"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.celrep.2014.03.011","article-title":"Evolution of Alu Elements toward Enhancers","volume":"7","author":"Su","year":"2014","journal-title":"Cell Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1016\/j.celrep.2017.11.019","article-title":"Enhancer SINEs Link Pol III to Pol II Transcription in Neurons","volume":"21","author":"Policarpi","year":"2017","journal-title":"Cell Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/nsmb.2400","article-title":"DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation","volume":"19","author":"Hu","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1038\/sj.onc.1201410","article-title":"Retinoic acid enhances the expression of interferon-induced proteins: Evidence for multiple mechanisms of action","volume":"15","author":"Pelicano","year":"1997","journal-title":"Oncogene"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1073\/pnas.74.12.5382","article-title":"Retinoic acid (vitamin A acid) induced transcriptional control of interferon production","volume":"74","author":"Blalock","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7463","DOI":"10.1074\/jbc.M115.636365","article-title":"RNA polymerase III regulates cytosolic RNA:DNA hybrids and intracellular microRNA expression","volume":"290","author":"Koo","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41586-022-05545-9","article-title":"R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response","volume":"613","author":"Crossley","year":"2023","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13100-024-00324-x","article-title":"Subcellular location of L1 retrotransposon-encoded ORF1p, reverse transcription products, and DNA sensors in lupus granulocytes","volume":"15","author":"Moadab","year":"2024","journal-title":"Mob. DNA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.15252\/embj.201488726","article-title":"Cytosolic RNA:DNA hybrids activate the cGAS-STING axis","volume":"33","author":"Mankan","year":"2014","journal-title":"EMBO J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41586-023-06947-z","article-title":"Structures, functions and adaptations of the human LINE-1 ORF2 protein","volume":"626","author":"Baldwin","year":"2024","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0014-5793(89)81667-9","article-title":"HSV infection induces increased transcription of Alu repeated sequences by RNA polymerase III","volume":"258","author":"Jang","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1126\/science.aac7442","article-title":"The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression","volume":"350","author":"Hung","year":"2015","journal-title":"Science"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10577-018-9573-4","article-title":"Warning SINEs: Alu elements, evolution of the human brain, and the spectrum of neurological disease","volume":"26","author":"Larsen","year":"2018","journal-title":"Chromosome Res."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Aune, T.M., Tossberg, J.T., Heinrich, R.M., Porter, K.P., and Crooke, P.S. (2022). Alu RNA Structural Features Modulate Immune Cell Activation and A-to-I Editing of Alu RNAs Is Diminished in Human Inflammatory Bowel Disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.818023"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-neuro-082823-020615","article-title":"The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders","volume":"47","author":"Frost","year":"2024","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"240080","DOI":"10.1098\/rsos.240080","article-title":"The ancient Z-DNA and Z-RNA specific Z\u03b1 fold has evolved modern roles in immunity and transcription through the natural selection of flipons","volume":"11","author":"Herbert","year":"2024","journal-title":"R. Soc. Open Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"7024","DOI":"10.1073\/pnas.84.20.7024","article-title":"Supercoiling of the DNA template during transcription","volume":"84","author":"Liu","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"250171","DOI":"10.1098\/rsob.250171","article-title":"The evolutionary entanglement of flipons with zinc fingers and retroelements has engendered a large family of Z-DNA and G-quadruplex binding proteins","volume":"15","author":"Herbert","year":"2025","journal-title":"Open Biol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Herbert, A. (2025). Control of Gene Expression by Proteins That Bind Many Alternative Nucleic Acid Structures Through the Same Domain. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010272"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cell.2009.04.049","article-title":"Centromeric nucleosomes induce positive DNA supercoils","volume":"138","author":"Furuyama","year":"2009","journal-title":"Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1101\/gr.158801","article-title":"Biased distribution of inverted and direct Alus in the human genome: Implications for insertion, exclusion, and genome stability","volume":"11","author":"Stenger","year":"2001","journal-title":"Genome Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e2200166","DOI":"10.1002\/bies.202200166","article-title":"Nucleosomes and flipons exchange energy to alter chromatin conformation, the readout of genomic information, and cell fate","volume":"44","author":"Herbert","year":"2022","journal-title":"Bioessays"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Lexa, M., Steflova, P., Martinek, T., Vorlickova, M., Vyskot, B., and Kejnovsky, E. (2014). Guanine quadruplexes are formed by specific regions of human transposable elements. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-1032"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"109500","DOI":"10.1016\/j.celrep.2021.109500","article-title":"ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation","volume":"36","author":"Dierick","year":"2021","journal-title":"Cell Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41586-022-04753-7","article-title":"ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis","volume":"606","author":"Zhang","year":"2022","journal-title":"Nature"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"522","DOI":"10.14348\/molcells.2022.0060","article-title":"Z-DNA-Containing Long Terminal Repeats of Human Endogenous Retrovirus Families Provide Alternative Promoters for Human Functional Genes","volume":"45","author":"Lee","year":"2022","journal-title":"Mol. Cells"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41586-025-09705-5","article-title":"Host cell Z-RNAs activate ZBP1 during virus infections","volume":"648","author":"Yin","year":"2025","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.molcel.2026.03.031","article-title":"Alu repeat-containing RNAs spatially organize actively transcribed genomic regions around nuclear speckles","volume":"86","author":"Liu","year":"2026","journal-title":"Mol. Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41586-023-06323-x","article-title":"Complementary Alu sequences mediate enhancer-promoter selectivity","volume":"619","author":"Liang","year":"2023","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41588-024-02025-w","article-title":"Gene regulation by convergent promoters","volume":"57","author":"Wiechens","year":"2025","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1038\/s41467-026-70296-4","article-title":"Integrated small and long RNA sequencing reveals piRNA mediated transposon repression during human oogenesis","volume":"17","author":"Zhang","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/s41586-023-06257-4","article-title":"Relaxed targeting rules help PIWI proteins silence transposons","volume":"619","author":"Gainetdinov","year":"2023","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cub.2009.12.044","article-title":"MicroRNA function is globally suppressed in mouse oocytes and early embryos","volume":"20","author":"Suh","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.cell.2013.10.001","article-title":"A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes","volume":"155","author":"Flemr","year":"2013","journal-title":"Cell"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Stein, P., Rozhkov, N.V., Li, F., Cardenas, F.L., Davydenko, O., Vandivier, L.E., Gregory, B.D., Hannon, G.J., and Schultz, R.M. (2015). Essential Role for endogenous siRNAs during meiosis in mouse oocytes. PLoS Genet., 11, Erratum in PLoS Genet.\u00a02015, 11, e1005129. https:\/\/doi.org\/10.1371\/journal.pgen.1005129. eCollection 2015 Apr. PMID: 25860788.","DOI":"10.1371\/journal.pgen.1005013"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.molcel.2021.11.005","article-title":"Seeking the truth behind the myth: Argonaute tales from \u201cnuclearland\u201d","volume":"82","author":"Nazer","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.tig.2017.08.006","article-title":"The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution","volume":"33","author":"Yang","year":"2017","journal-title":"Trends Genet."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1101\/gr.384802","article-title":"Active Alu element \u201cA-tails\u201d: Size does matter","volume":"12","author":"Salem","year":"2002","journal-title":"Genome Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/s41556-022-01008-5","article-title":"KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA-DNA triplexes and HP1 binding","volume":"24","author":"Zhang","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.1093\/nar\/gkh818","article-title":"Over 20% of human transcripts might form sense-antisense pairs","volume":"32","author":"Chen","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"8917","DOI":"10.1093\/nar\/gks654","article-title":"Epigenetic control of alternative mRNA processing at the imprinted Herc3\/Nap1l5 locus","volume":"40","author":"Cowley","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4161\/trns.2.1.13511","article-title":"Transcriptional interference by RNA polymerase pausing and dislodgement of transcription factors","volume":"2","author":"Palmer","year":"2011","journal-title":"Transcription"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1534\/genetics.106.069484","article-title":"Transcriptional interferences in cis natural antisense transcripts of humans and mice","volume":"176","author":"Osato","year":"2007","journal-title":"Genetics"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.molcel.2020.12.014","article-title":"Integrator is a genome-wide attenuator of non-productive transcription","volume":"81","author":"Zumer","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Herbert, A., Pavlov, F., Konovalov, D., and Poptsova, M. (2023). Conserved microRNAs and Flipons Shape Gene Expression during Development by Altering Promoter Conformations. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054884"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/363561a0","article-title":"A tetrameric DNA structure with protonated cytosine-cytosine base pairs","volume":"363","author":"Gehring","year":"1993","journal-title":"Nature"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3270","DOI":"10.1073\/pnas.0807699106","article-title":"A Z-DNA sequence reduces slipped-strand structure formation in the myotonic dystrophy type 2 (CCTG)\u00b7(CAGG) repeat","volume":"106","author":"Edwards","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Herbert, A. (2026). The Chromaverse Is Colored by Triplexes Formed Through the Interactions of Noncoding RNAs with HNPRNPU, TP53, AGO, REL Proteins, Intrinsically-Disordered Regions, and Flipons. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031482"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/nbt996","article-title":"Systematic identification of abundant A-to-I editing sites in the human transcriptome","volume":"22","author":"Levanon","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1101\/gr.2855504","article-title":"Widespread RNA editing of embedded alu elements in the human transcriptome","volume":"14","author":"Kim","year":"2004","journal-title":"Genome Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1101\/gr.2951204","article-title":"A survey of RNA editing in human brain","volume":"14","author":"Blow","year":"2004","journal-title":"Genome Res."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Athanasiadis, A., Rich, A., and Maas, S. (2004). Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol., 2.","DOI":"10.1371\/journal.pbio.0020391"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/s41467-017-01458-8","article-title":"RNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure","volume":"8","author":"Solomon","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"a035352","DOI":"10.1101\/cshperspect.a035352","article-title":"Mapping the dsRNA World","volume":"11","author":"Reich","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrm.2015.4","article-title":"A-to-I editing of coding and non-coding RNAs by ADARs","volume":"17","author":"Nishikura","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature24041","article-title":"Dynamic landscape and regulation of RNA editing in mammals","volume":"550","author":"Tan","year":"2017","journal-title":"Nature"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1126\/science.aad5497","article-title":"Regulatory evolution of innate immunity through co-option of endogenous retroviruses","volume":"351","author":"Chuong","year":"2016","journal-title":"Science"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Herbert, A. (2021). To \u201cZ\u201d or not to \u201cZ\u201d: Z-RNA, self-recognition, and the MDA5 helicase. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009513"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1126\/science.aac7049","article-title":"RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself","volume":"349","author":"Liddicoat","year":"2015","journal-title":"Science"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.1074\/jbc.M311347200","article-title":"Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1","volume":"279","author":"Hartner","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1073\/pnas.1017241108","article-title":"RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis","volume":"108","author":"Ward","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1006\/viro.1995.1370","article-title":"Mechanism of interferon action: Double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons","volume":"210","author":"Patterson","year":"1995","journal-title":"Virology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41431-019-0458-6","article-title":"Mendelian disease caused by variants affecting recognition of Z-DNA and Z-RNA by the Za domain of the double-stranded RNA editing enzyme ADAR","volume":"28","author":"Herbert","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.chom.2021.05.009","article-title":"Vaccinia virus E3 prevents sensing of Z-RNA to block ZBP1-dependent necroptosis","volume":"29","author":"Koehler","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/s41586-022-04974-w","article-title":"ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation","volume":"607","author":"Verdonck","year":"2022","journal-title":"Nature"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41586-022-04896-7","article-title":"ADAR1 mutation causes ZBP1-dependent immunopathology","volume":"607","author":"Hubbard","year":"2022","journal-title":"Nature"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41586-022-04878-9","article-title":"ADAR1 averts fatal type I interferon induction by ZBP1","volume":"607","author":"Jiao","year":"2022","journal-title":"Nature"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e180451","DOI":"10.1172\/JCI180451","article-title":"ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia\/reperfusion injury","volume":"134","author":"Liu","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"eaea3979","DOI":"10.1126\/sciadv.aea3979","article-title":"Innate immune sensing of dietary alcohol ignites inflammation to drive alcohol-related disease","volume":"12","author":"Jang","year":"2026","journal-title":"Sci. Adv."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"9505","DOI":"10.1074\/jbc.M109488200","article-title":"Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3","volume":"277","author":"Sun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"6427","DOI":"10.4049\/jimmunol.181.9.6427","article-title":"Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors","volume":"181","author":"Kaiser","year":"2008","journal-title":"J. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cell.2012.06.019","article-title":"The RIP1\/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis","volume":"150","author":"Li","year":"2012","journal-title":"Cell"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1038\/s44319-026-00866-6","article-title":"Human ZBP1 is a potent inducer of cell death through mechanisms divergent from mouse ZBP1","volume":"27","author":"Lu","year":"2026","journal-title":"EMBO Rep."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"117113","DOI":"10.1016\/j.celrep.2026.117113","article-title":"Aberrant multicellular interferon signaling underlies Adar1 mutation-driven Aicardi-Goutieres syndrome-like encephalopathy","volume":"45","author":"Yoo","year":"2026","journal-title":"Cell Rep."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41586-020-2844-1","article-title":"Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency","volume":"588","author":"Mehdipour","year":"2020","journal-title":"Nature"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1158\/2159-8290.CD-25-2164","article-title":"Transposable Element Activation: A Hallmark of Cancer","volume":"16","author":"Chiappinelli","year":"2026","journal-title":"Cancer Discov."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"6428","DOI":"10.1038\/s41467-026-73211-z","article-title":"m6A modification suppresses innate anti-tumour immunity in colorectal cancer by limiting alu-derived dsRNA accumulation","volume":"17","author":"Wang","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nature09701","article-title":"LncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3\u2032 UTRs via Alu elements","volume":"470","author":"Gong","year":"2011","journal-title":"Nature"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1016\/j.molcel.2024.11.022","article-title":"Circular RNAs trigger nonsense-mediated mRNA decay","volume":"84","author":"Boo","year":"2024","journal-title":"Mol. Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2019.03.046","article-title":"Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity","volume":"177","author":"Liu","year":"2019","journal-title":"Cell"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.immuni.2018.03.016","article-title":"A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion","volume":"48","author":"Xia","year":"2018","journal-title":"Immunity"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"8996","DOI":"10.1039\/C5OB01340B","article-title":"Novel insights into a major DNA oxidative lesion: Its effects on Z-DNA stabilization","volume":"13","author":"Wang","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1021\/acs.chemrestox.9b00041","article-title":"Oxidative Modification of Guanine in a Potential Z-DNA-Forming Sequence of a Gene Promoter Impacts Gene Expression","volume":"32","author":"Fleming","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"8056","DOI":"10.1021\/acsomega.0c00120","article-title":"Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers","volume":"5","author":"Vongsutilers","year":"2020","journal-title":"ACS Omega"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1016\/j.cell.2023.05.039","article-title":"Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity","volume":"186","author":"Lei","year":"2023","journal-title":"Cell"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"105140","DOI":"10.1016\/j.jbc.2023.105140","article-title":"Flipons and small RNAs accentuate the asymmetries of pervasive transcription by the reset and sequence-specific microcoding of promoter conformation","volume":"299","author":"Herbert","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41576-022-00539-9","article-title":"Dynamic alternative DNA structures in biology and disease","volume":"24","author":"Wang","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature21715","article-title":"DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome","volume":"544","author":"Aktas","year":"2017","journal-title":"Nature"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s13365-026-01324-8","article-title":"The emerging role of circular RNAs in neurodegenerative diseases and viral infections","volume":"32","author":"Medina","year":"2026","journal-title":"J. Neurovirol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/j.celrep.2018.04.025","article-title":"RNA\/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage","volume":"23","author":"Cristini","year":"2018","journal-title":"Cell Rep."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"D\u2019Augustin, O., Huet, S., Campalans, A., and Radicella, J.P. (2020). Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218360"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Herbert, A., and Poptsova, M. (2022). Z-RNA and the Flipside of the SARS Nsp13 Helicase: Is There a Role for Flipons in Coronavirus-Induced Pathology?. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.912717"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"111444","DOI":"10.1016\/j.isci.2024.111444","article-title":"Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling","volume":"27","author":"Mishra","year":"2024","journal-title":"iScience"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e2500208122","DOI":"10.1073\/pnas.2500208122","article-title":"SARS-CoV-2 infection induces ZBP1-dependent PANoptosis in bystander cells","volume":"122","author":"Yang","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"e03977","DOI":"10.1002\/advs.202503977","article-title":"The NSP5, ORF6 and NSP13 of SARS-CoV-2 Cooperate to Modulate Inflammatory Cell Death Activation","volume":"12","author":"Wang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-023-06889-6","article-title":"MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis","volume":"625","author":"Cho","year":"2024","journal-title":"Nature"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"101319","DOI":"10.1016\/j.drup.2025.101319","article-title":"ZBP1 antagonizes MRE11-mediated DNA end resection and confers synthetic lethality to PARP inhibition in ovarian cancer","volume":"84","author":"Shi","year":"2026","journal-title":"Drug Resist. Updates"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.7150\/ijbs.122290","article-title":"Neutrophil extracellular traps prime the ZBP1-cGAS sensor complex, triggering necroptosis and inflammatory injury in acute pancreatitis","volume":"22","author":"Zhang","year":"2026","journal-title":"Int. J. Biol. Sci."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/ard-2023-225266","article-title":"The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon","volume":"83","author":"Pisetsky","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.molcel.2018.08.047","article-title":"Genome-wide Identification of Structure-Forming Repeats as Principal Sites of Fork Collapse upon ATR Inhibition","volume":"72","author":"Shastri","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/s41586-023-05710-8","article-title":"Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis","volume":"614","author":"Nassour","year":"2023","journal-title":"Nature"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1016\/j.jmb.2014.05.001","article-title":"Novel interaction of the Z-DNA binding domain of human ADAR1 with the oncogenic c-Myc promoter G-quadruplex","volume":"426","author":"Kang","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1038\/s41467-026-69989-7","article-title":"Telomeric repeat-containing RNA G-quadruplexes trigger ZBP1-mediated cell death","volume":"17","author":"Qin","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Herbert, A. (2021). The Simple Biology of Flipons and Condensates Enhances the Evolution of Complexity. Molecules, 26.","DOI":"10.3390\/molecules26164881"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1146\/annurev.bi.53.070184.004043","article-title":"The Chemistry and Biology of Left-Handed Z-DNA","volume":"53","author":"Rich","year":"1984","journal-title":"Annu. Rev. Biochem."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Barba-Aliaga, M., Alepuz, P., and Perez-Ortin, J.E. (2021). Eukaryotic RNA Polymerases: The Many Ways to Transcribe a Gene. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.663209"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.cell.2024.12.013","article-title":"An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development","volume":"188","author":"Oomen","year":"2025","journal-title":"Cell"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8526\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:14:35Z","timestamp":1790241275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":210,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198526"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198526","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}