{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:58:29Z","timestamp":1792213109885,"version":"4.4.0"},"reference-count":108,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016608","name":"Rainwater Charitable Foundation","doi-asserted-by":"publisher","award":["NS097850"],"award-info":[{"award-number":["NS097850"]}],"id":[{"id":"10.13039\/100016608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OAC1920103"],"award-info":[{"award-number":["OAC1920103"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS113636"],"award-info":[{"award-number":["NS113636"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS128494"],"award-info":[{"award-number":["NS128494"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HG009518"],"award-info":[{"award-number":["HG009518"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS110098"],"award-info":[{"award-number":["NS110098"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS074324"],"award-info":[{"award-number":["NS074324"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM149729"],"award-info":[{"award-number":["GM149729"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS089616"],"award-info":[{"award-number":["NS089616"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012443","name":"Maryland Stem Cell Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016948","name":"Tau Consortium","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016948","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012312","name":"Johns Hopkins University Robert Packard Center for ALS Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003194","name":"New York Stem Cell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019250","name":"John Douglas French Alzheimer&apos;s Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019250","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuron"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.neuron.2025.12.005","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T15:53:36Z","timestamp":1770220416000},"page":"1045-1065.e13","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexes"],"prefix":"10.1016","volume":"114","author":[{"given":"Honghe","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapas","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ning","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haocheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yatao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongfan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Periz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin K.","family":"Ichida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sua","family":"Myong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkai","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9115-8708","authenticated-orcid":false,"given":"Jiou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuron.2025.12.005_bib1","series-title":"Tandem Repeat Polymorphisms: Genetic Plasticity, Neural Diversity and Disease","first-page":"1","article-title":"Tandem Repeat Polymorphisms","author":"Hannan","year":"2012"},{"key":"10.1016\/j.neuron.2025.12.005_bib2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.neuro.29.051605.113014","article-title":"RNA-mediated neuromuscular disorders","volume":"29","author":"Ranum","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"10.1016\/j.neuron.2025.12.005_bib3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2025.12.005_bib4","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2025.12.005_bib5","doi-asserted-by":"crossref","first-page":"2950.e5","DOI":"10.1016\/j.neurobiolaging.2012.07.005","article-title":"Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype","volume":"33","author":"Rutherford","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuron.2025.12.005_bib6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainres.2016.04.004","article-title":"There has been an awakening: Emerging mechanisms of C9orf72 mutations in FTD\/ALS","volume":"1647","author":"Gitler","year":"2016","journal-title":"Brain Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib7","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.neuron.2023.01.022","article-title":"DNA-initiated epigenetic cascades driven by C9orf72 hexanucleotide repeat","volume":"111","author":"Liu","year":"2023","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2025.12.005_bib8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.chembiol.2016.12.018","article-title":"c9orf72 Disease-Related Foci Are Each Composed of One Mutant Expanded Repeat RNA","volume":"24","author":"Liu","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib9","doi-asserted-by":"crossref","first-page":"E4530","DOI":"10.1073\/pnas.1318835110","article-title":"Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration","volume":"110","author":"Lagier-Tourenne","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2025.12.005_bib10","first-page":"7421","article-title":"G-quadruplexes offer a conserved structural motif for NONO recruitment to NEAT1 architectural lncRNA","volume":"48","author":"Simko","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature14973","article-title":"The C9orf72 repeat expansion disrupts nucleocytoplasmic transport","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2025.12.005_bib12","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.17820","article-title":"The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains","volume":"5","author":"Conlon","year":"2016","journal-title":"eLife"},{"key":"10.1016\/j.neuron.2025.12.005_bib13","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1016\/j.neuron.2024.07.025","article-title":"Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD\/ALS","volume":"112","author":"Wu","year":"2024","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2025.12.005_bib14","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1016\/j.neuron.2024.10.001","article-title":"Interference of nuclear speckles: A nexus of RNA foci, dipeptide repeats, and mis-splicing in C9ORF72 ALS\/FTD","volume":"112","author":"Zhu","year":"2024","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2025.12.005_bib15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00401-017-1798-3","article-title":"Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated ALS\/FTD","volume":"135","author":"Moens","year":"2018","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2025.12.005_bib16","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00401-017-1796-5","article-title":"A zebrafish model for C9orf72 ALS reveals RNA toxicity as a pathogenic mechanism","volume":"135","author":"Swinnen","year":"2018","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2025.12.005_bib17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00401-017-1725-7","article-title":"In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers","volume":"134","author":"DeJesus-Hernandez","year":"2017","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuron.2025.12.005_bib18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41576-019-0135-1","article-title":"Chromatin-associated RNAs as facilitators of functional genomic interactions","volume":"20","author":"Li","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.neuron.2025.12.005_bib19","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1016\/j.cell.2021.10.014","article-title":"RNA promotes the formation of spatial compartments in the nucleus","volume":"184","author":"Quinodoz","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2025.12.005_bib20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.chembiol.2018.10.018","article-title":"The Hairpin Form of r(G4C2)exp in c9ALS\/FTD Is Repeat-Associated Non-ATG Translated and a Target for Bioactive Small Molecules","volume":"26","author":"Wang","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nature13124","article-title":"C9orf72 nucleotide repeat structures initiate molecular cascades of disease","volume":"507","author":"Haeusler","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2025.12.005_bib22","doi-asserted-by":"crossref","first-page":"7368","DOI":"10.1021\/jacs.1c00131","article-title":"A Helicase Unwinds Hexanucleotide Repeat RNA G-Quadruplexes and Facilitates Repeat-Associated Non-AUG Translation","volume":"143","author":"Liu","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.neuron.2025.12.005_bib23","doi-asserted-by":"crossref","first-page":"9860","DOI":"10.1074\/jbc.C113.452532","article-title":"The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures","volume":"288","author":"Reddy","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neuron.2025.12.005_bib24","doi-asserted-by":"crossref","DOI":"10.3791\/3912-v","article-title":"Chromatin isolation by RNA purification (ChIRP)","author":"Chu","year":"2012","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.neuron.2025.12.005_bib25","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1038\/s41593-025-02039-5","article-title":"Aberrant splicing exonizes C9orf72 repeat expansion in ALS\/FTD","volume":"28","author":"Yang","year":"2025","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2025.12.005_bib26","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2507334122","article-title":"Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation","volume":"122","author":"Miller","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2025.12.005_bib27","doi-asserted-by":"crossref","first-page":"E4968","DOI":"10.1073\/pnas.1315438110","article-title":"RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia","volume":"110","author":"Zu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2025.12.005_bib28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40478-016-0306-7","article-title":"C9orf72 is differentially expressed in the central nervous system and myeloid cells and consistently reduced in C9orf72, MAPT and GRN mutation carriers","volume":"4","author":"Rizzu","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.neuron.2025.12.005_bib29","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.cell.2023.01.005","article-title":"PIKFYVE inhibition mitigates disease in models of diverse forms of ALS","volume":"186","author":"Hung","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2025.12.005_bib30","doi-asserted-by":"crossref","DOI":"10.1080\/19336950.2025.2480713","article-title":"Electrophysiological characterization of sourced human iPSC-derived motor neurons","volume":"19","author":"Jurkovicova-Tarabova","year":"2025","journal-title":"Channels (Austin)"},{"key":"10.1016\/j.neuron.2025.12.005_bib31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-1-4939-2253-6_11","article-title":"RNA antisense purification (RAP) for mapping RNA interactions with chromatin","volume":"1262","author":"Engreitz","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib32","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aai7866","article-title":"Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis","volume":"9","author":"Gendron","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2025.12.005_bib33","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41593-022-01205-3","article-title":"Integrative transcriptomic analysis of the amyotrophic lateral sclerosis spinal cord implicates glial activation and suggests new risk genes","volume":"26","author":"Humphrey","year":"2023","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2025.12.005_bib34","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nrc2222","article-title":"Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis","volume":"7","author":"Menendez","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.neuron.2025.12.005_bib35","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1101\/gad.315564.118","article-title":"A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-induced nutrient stress","volume":"32","author":"Liu","year":"2018","journal-title":"Genes Dev."},{"key":"10.1016\/j.neuron.2025.12.005_bib36","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1038\/s41593-021-00944-z","article-title":"Multi-omic analysis of selectively vulnerable motor neuron subtypes implicates altered lipid metabolism in ALS","volume":"24","author":"Lee","year":"2021","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2025.12.005_bib37","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.cmet.2021.01.005","article-title":"C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly","volume":"33","author":"Wang","year":"2021","journal-title":"Cell Metab."},{"key":"10.1016\/j.neuron.2025.12.005_bib38","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1021\/acssynbio.2c00156","article-title":"Quantification of Genome Editing and Transcriptional Control Capabilities Reveals Hierarchies among Diverse CRISPR\/Cas Systems in Human Cells","volume":"11","author":"Escobar","year":"2022","journal-title":"ACS Synth. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib39","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cca.2011.02.013","article-title":"Advances in DNA methylation: 5-hydroxymethylcytosine revisited","volume":"412","author":"Dahl","year":"2011","journal-title":"Clin. Chim. Acta; Int. J. Clin. Chem."},{"key":"10.1016\/j.neuron.2025.12.005_bib40","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-23142-8","article-title":"Impact of DNA methylation on 3D genome structure","volume":"12","author":"Buitrago","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2025.12.005_bib41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/gb-2003-4-2-206","article-title":"Sp1- and Kruppel-like transcription factors","volume":"4","author":"Kaczynski","year":"2003","journal-title":"Genome Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib42","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-18035-1","article-title":"ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation","volume":"11","author":"Bentsen","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2025.12.005_bib43","article-title":"Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation","volume":"14","author":"Li","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2025.12.005_bib44","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1093\/nar\/gkt264","article-title":"Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control","volume":"41","author":"Zheng","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib45","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1021\/ja4085572","article-title":"Mechanism and manipulation of DNA:RNA hybrid G-quadruplex formation in transcription of G-rich DNA","volume":"136","author":"Zhang","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.neuron.2025.12.005_bib46","doi-asserted-by":"crossref","first-page":"7171","DOI":"10.1002\/anie.201709184","article-title":"G-Quadruplex Secondary Structure Obtained from Circular Dichroism Spectroscopy","volume":"57","author":"Del Villar-Guerra","year":"2018","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.neuron.2025.12.005_bib47","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/978-1-4939-9666-7_18","article-title":"G-Quadruplex and Protein Binding by Single-Molecule FRET Microscopy","volume":"2035","author":"Lee","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fchem.2016.00038","article-title":"Metal Cations in G-Quadruplex Folding and Stability","volume":"4","author":"Bhattacharyya","year":"2016","journal-title":"Front. Chem."},{"key":"10.1016\/j.neuron.2025.12.005_bib49","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1093\/nar\/gkf540","article-title":"RNA canonical and non-canonical base pairing types: a recognition method and complete repertoire","volume":"30","author":"Lemieux","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib50","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.tibs.2024.03.009","article-title":"RNA-DNA triplexes: molecular mechanisms and functional relevance","volume":"49","author":"Leisegang","year":"2024","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.neuron.2025.12.005_bib51","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4939-6716-2_13","article-title":"Detection and Characterization of R Loop Structures","volume":"1543","author":"Boque-Sastre","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nsmb0208-123","article-title":"DNA torsional stress propagates through chromatin fiber and participates in transcriptional regulation","volume":"15","author":"Lavelle","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib53","doi-asserted-by":"crossref","first-page":"7144","DOI":"10.1093\/nar\/gkt443","article-title":"DNA G-quadruplex formation in response to remote downstream transcription activity: long-range sensing and signal transducing in DNA double helix","volume":"41","author":"Zhang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib54","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1158\/1535-7163.MCT-09-0549","article-title":"Triptolide is an inhibitor of RNA polymerase I and II-dependent transcription leading predominantly to down-regulation of short-lived mRNA","volume":"8","author":"Visp\u00e9","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.neuron.2025.12.005_bib55","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1016\/j.jmb.2020.02.014","article-title":"Ultra-deep Coverage Single-molecule R-loop Footprinting Reveals Principles of R-loop Formation","volume":"432","author":"Malig","year":"2020","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib56","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000071","article-title":"Screening for novel hexanucleotide repeat expansions at ALS- and FTD-associated loci","volume":"2","author":"He","year":"2016","journal-title":"Neurol. Genet."},{"key":"10.1016\/j.neuron.2025.12.005_bib57","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1038\/s41596-019-0159-1","article-title":"High-resolution, strand-specific R-loop mapping via S9.6-based DNA-RNA immunoprecipitation and high-throughput sequencing","volume":"14","author":"Sanz","year":"2019","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.neuron.2025.12.005_bib58","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":"10.1016\/j.neuron.2025.12.005_bib59","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nchem.1805","article-title":"Visualization and selective chemical targeting of RNA G-quadruplex structures in the cytoplasm of human cells","volume":"6","author":"Biffi","year":"2014","journal-title":"Nat. Chem."},{"key":"10.1016\/j.neuron.2025.12.005_bib60","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2022.101892","article-title":"Protocol to assess RNA-RNA interactions in situ using an RNA-proximity ligation assay","volume":"3","author":"Basavappa","year":"2022","journal-title":"Star Protoc."},{"key":"10.1016\/j.neuron.2025.12.005_bib61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/10409238.2020.1841726","article-title":"Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies","volume":"56","author":"Schwartz","year":"2021","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib62","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41582-018-0047-2","article-title":"C9orf72-mediated ALS and FTD: multiple pathways to disease","volume":"14","author":"Balendra","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2025.12.005_bib63","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/nn.4065","article-title":"Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS","volume":"18","author":"Prudencio","year":"2015","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2025.12.005_bib64","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1093\/brain\/awae168","article-title":"Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward","volume":"147","author":"Cammack","year":"2024","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2025.12.005_bib65","doi-asserted-by":"crossref","DOI":"10.1172\/JCI179016","article-title":"CRISPR\/Cas13d targeting suppresses repeat-associated non-AUG translation of C9orf72 hexanucleotide repeat RNA","volume":"134","author":"Liu","year":"2024","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.neuron.2025.12.005_bib66","doi-asserted-by":"crossref","first-page":"10473","DOI":"10.1093\/nar\/gku658","article-title":"Processing of double-R-loops in (CAG)\u00b7(CTG) and C9orf72 (GGGGCC)\u00b7(GGCCCC) Repeats Causes Instability","volume":"42","author":"Reddy","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib67","doi-asserted-by":"crossref","first-page":"8521","DOI":"10.1021\/jacs.5b03413","article-title":"Visualization of RNA-Quadruplexes in Live Cells","volume":"137","author":"Laguerre","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.neuron.2025.12.005_bib68","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1039\/C5SC03946K","article-title":"RNA G-quadruplex formation in defined sequence in living cells detected by bimolecular fluorescence complementation","volume":"7","author":"Liu","year":"2016","journal-title":"Chem. Sci."},{"key":"10.1016\/j.neuron.2025.12.005_bib69","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2401099121","article-title":"Dominant and genome-wide formation of DNA:RNA hybrid G-quadruplexes in living yeast cells","volume":"121","author":"Ren","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2025.12.005_bib70","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1126\/science.1245831","article-title":"Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome","volume":"343","author":"Colak","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.neuron.2025.12.005_bib71","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.chembiol.2016.09.011","article-title":"RNA-DNA Triplex Formation by Long Noncoding RNAs","volume":"23","author":"Li","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.neuron.2025.12.005_bib72","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cell.2017.06.017","article-title":"TERRA RNA Antagonizes ATRX and Protects Telomeres","volume":"170","author":"Chu","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2025.12.005_bib73","doi-asserted-by":"crossref","first-page":"13110","DOI":"10.1002\/anie.201407045","article-title":"Formation of DNA:RNA hybrid G-quadruplexes of two G-quartet layers in transcription: expansion of the prevalence and diversity of G-quadruplexes in genomes","volume":"53","author":"Xiao","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.neuron.2025.12.005_bib74","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1093\/brain\/awab449","article-title":"Motor neuron pathology in CANVAS due to RFC1 expansions","volume":"145","author":"Huin","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.neuron.2025.12.005_bib75","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1002\/mds.29183","article-title":"Repeat-Associated Non-AUG Translation of AGAGGG Repeats that Cause X-Linked Dystonia-Parkinsonism","volume":"37","author":"Reyes","year":"2022","journal-title":"Mov. Disord."},{"key":"10.1016\/j.neuron.2025.12.005_bib76","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ajhg.2011.05.015","article-title":"Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement","volume":"89","author":"Kobayashi","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.neuron.2025.12.005_bib77","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1042\/BST20200690","article-title":"Mechanisms of repeat-associated non-AUG translation in neurological microsatellite expansion disorders","volume":"49","author":"Castelli","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.neuron.2025.12.005_bib78","doi-asserted-by":"crossref","first-page":"10832","DOI":"10.1093\/nar\/gku764","article-title":"A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the mitochondrial transcription termination at the DNA replication priming site","volume":"42","author":"Zheng","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib79","article-title":"DNA:RNA hybrid G-quadruplex formation upstream of transcription start site","volume":"10","author":"Zhang","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2025.12.005_bib80","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1016\/j.bmc.2014.05.053","article-title":"Finding a human telomere DNA-RNA hybrid G-quadruplex formed by human telomeric 6-mer RNA and 16-mer DNA using click chemistry: a protective structure for telomere end","volume":"22","author":"Xu","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.neuron.2025.12.005_bib81","doi-asserted-by":"crossref","first-page":"10334","DOI":"10.1093\/nar\/gks802","article-title":"A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop","volume":"40","author":"Wanrooij","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib87","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.cell.2006.01.040","article-title":"A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen","volume":"124","author":"Moffat","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2025.12.005_bib89","unstructured":"Krueger F., James F., Ewels P., Afyounian E., and Schuster-Boeckler B. FelixKrueger\/TrimGalore, v0.6.7. 2021. https:\/\/doi.org\/10.5281\/zenodo.5127899."},{"key":"10.1016\/j.neuron.2025.12.005_bib90","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nature methods"},{"key":"10.1016\/j.neuron.2025.12.005_bib91","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib92","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib93","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: Precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"Law","year":"2014","journal-title":"Genome Biol"},{"key":"10.1016\/j.neuron.2025.12.005_bib94","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","article-title":"A comparison of normalization methods for high density oligonucleotide array data based on variance and bias","volume":"19","author":"Bolstad","year":"2003","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib95","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory- efficient alignment of short DNA sequences to the human genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome biology"},{"key":"10.1016\/j.neuron.2025.12.005_bib96","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome biology"},{"key":"10.1016\/j.neuron.2025.12.005_bib97","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1093\/bioinformatics\/btv145","article-title":"ChIPseeker: an R\/Bioconductor package for ChIP peak annotation, comparison and visualization","volume":"31","author":"Yu","year":"2015","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib98","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol Cell"},{"key":"10.1016\/j.neuron.2025.12.005_bib99","doi-asserted-by":"crossref","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep- sequencing data analysis","volume":"44","author":"Ramirez","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.neuron.2025.12.005_bib100","author":"Shen"},{"key":"10.1016\/j.neuron.2025.12.005_bib101","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","article-title":"circlize Implements and enhances circular visualization in R","volume":"30","author":"Gu","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib102","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nature10730","article-title":"Differential oestrogen receptor binding is associated with clinical outcome in breast cancer","volume":"481","author":"Ross-Innes","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2025.12.005_bib103","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/bioinformatics\/btv562","article-title":"regioneR: an R\/Bioconductor package for the association analysis of genomic regions based on permutation tests","volume":"32","author":"Gel","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib104","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-017-1708-7","article-title":"Intervene: a tool for intersection and visualization of multiple gene or genomic region sets","volume":"18","author":"Khan","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib105","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/bioinformatics\/btaa692","article-title":"pyGenomeTracks: reproducible plots for multivariate genomic datasets","volume":"37","author":"Lopez-Delisle","year":"2021","journal-title":"Bioinformatics"},{"key":"10.1016\/j.neuron.2025.12.005_bib106","doi-asserted-by":"crossref","first-page":"695124","DOI":"10.3389\/fgene.2021.695124","article-title":"Folate Deficiency Triggers the Abnormal Segregation of a Region With Large Cluster of CG-Rich Trinucleotide Repeats on Human Chromosome 2","volume":"12","author":"Garribba","year":"2021","journal-title":"Front Genet"},{"key":"10.1016\/j.neuron.2025.12.005_bib107","doi-asserted-by":"crossref","first-page":"D174","DOI":"10.1093\/nar\/gkad1059","article-title":"JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles","volume":"52","author":"Rauluseviciute","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.neuron.2025.12.005_bib108","doi-asserted-by":"crossref","first-page":"D252","DOI":"10.1093\/nar\/gkx1106","article-title":"HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis","volume":"46","author":"Kulakovskiy","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.neuron.2025.12.005_bib82","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.neuron.2025.12.005_bib83","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.cell.2017.07.010","article-title":"Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9","volume":"170","author":"Batra","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2025.12.005_bib84","doi-asserted-by":"crossref","first-page":"12377","DOI":"10.1093\/nar\/gkab1123","article-title":"TRF2 promotes dynamic and stepwise looping of POT1 bound telomeric overhang","volume":"49","author":"Paul","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.neuron.2025.12.005_bib85","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/j.bpj.2021.02.031","article-title":"Regeneration of PEG slide for multiple rounds of single-molecule measurements","volume":"120","author":"Paul","year":"2021","journal-title":"Biophys. J."},{"key":"10.1016\/j.neuron.2025.12.005_bib86","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nmeth.1208","article-title":"A practical guide to single-molecule FRET","volume":"5","author":"Roy","year":"2008","journal-title":"Nat. Methods"},{"key":"10.1016\/j.neuron.2025.12.005_bib88","article-title":"Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."}],"container-title":["Neuron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627325009328?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627325009328?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:11:55Z","timestamp":1790280715000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896627325009328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":108,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S0896627325009328"],"URL":"https:\/\/doi.org\/10.1016\/j.neuron.2025.12.005","relation":{},"ISSN":["0896-6273"],"issn-type":[{"value":"0896-6273","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexes","name":"articletitle","label":"Article Title"},{"value":"Neuron","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuron.2025.12.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}