{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:55:56Z","timestamp":1791284156607,"version":"4.1.0"},"reference-count":138,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Long non-coding RNAs (lncRNAs) have emerged as important regulators of innate immunity, acting across multiple molecular layers to shape antiviral and inflammatory responses. Among their diverse functions, protein-centered regulation provides a particularly versatile means of controlling immune signaling by altering the functional state, interactions, localization, or turnover of proteins without necessarily changing their transcription. In this review, we synthesize current evidence for lncRNA-mediated protein regulation in innate immunity and propose a protein-centered framework that connects molecular regulatory mechanisms with their functional and immunological consequences. At the mechanistic level, lncRNA\u2013protein interactions can modulate post-translational modifications, alter protein conformations, and facilitate or disrupt protein\u2013protein interactions. These regulatory modes, in turn, affect four major properties of immune proteins: protein stability, subcellular localization, molecular activity, and protein\u2013protein interaction-dependent signal transmission, ultimately reshaping innate immune responses. Across these mechanisms, several recurrent principles emerge, including preferential regulation of functionally important signaling nodes, integration of multiple regulatory mechanisms, and strong dependence on cellular and immunological context. Emerging evidence further suggests that some lncRNAs may act on defined protein states or regulatory interfaces without altering total protein abundance, although the generality of such functional selectivity remains to be established. Together, these findings support a hierarchical model in which lncRNAs translate specific molecular interactions into changes in protein function and, ultimately, innate immune states. This framework provides a basis for understanding how lncRNA\u2013protein interactions contribute to the fine-tuning of innate immunity and for evaluating their potential as targets for selective immune modulation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1994058","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:36:43Z","timestamp":1791283003000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["LncRNA\u2013protein interactions: molecular switches for the precise regulation of innate immunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Chenhao","family":"Yang","sequence":"first","affiliation":[{"name":"School of Bioengineering, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Feng","sequence":"additional","affiliation":[{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengfang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Bioengineering, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"He","sequence":"additional","affiliation":[{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linglong","family":"Xu","sequence":"additional","affiliation":[{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Qiao","sequence":"additional","affiliation":[{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"State Ethnic Affairs Commission Key Laboratory of Bioengineering and Technology, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Wang","sequence":"additional","affiliation":[{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"State Ethnic Affairs Commission Key Laboratory of Bioengineering and Technology, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Ministry of Education Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"Gansu Animal Cell Technology Innovation Center, Northwest Minzu University","place":["Lanzhou, China"]},{"name":"State Ethnic Affairs Commission Key Laboratory of Bioengineering and Technology, Northwest Minzu University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nature05874","article-title":"Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project","volume":"447","year":"2007","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003569","article-title":"Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs","volume":"9","author":"Hangauer","year":"2013","journal-title":"PloS Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00566-8","article-title":"Long non-coding RNAs: definitions, functions, challenges and recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-051410-092902","article-title":"Genome regulation by long noncoding RNAs","volume":"81","author":"Rinn","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1101\/gr.132159.111","article-title":"The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression","volume":"22","author":"Derrien","year":"2012","journal-title":"Genome Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1101\/gad.17446611","article-title":"Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses","volume":"25","author":"Cabili","year":"2011","journal-title":"Genes Dev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nature10887","article-title":"Modular regulatory principles of large non-coding RNAs","volume":"482","author":"Guttman","year":"2012","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904715106","article-title":"Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression","volume":"106","author":"Khalil","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192002","article-title":"Long noncoding RNA as modular scaffold of histone modification complexes","volume":"329","author":"Tsai","year":"2010","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3771","article-title":"Gene regulation in the immune system by long noncoding RNAs","volume":"18","author":"Chen","year":"2017","journal-title":"Nat Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrm3679","article-title":"RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts","volume":"14","author":"Geisler","year":"2013","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature06246","article-title":"Recognition of microorganisms and activation of the immune response","volume":"449","author":"Medzhitov","year":"2007","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003","article-title":"Immune signaling by RIG-I-like receptors","volume":"34","author":"Loo","year":"2011","journal-title":"Immunity"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00734.x","article-title":"Function of Nod-like receptors in microbial recognition and host defense","volume":"227","author":"Franchi","year":"2009","journal-title":"Immunol Rev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nri3446","article-title":"The history of Toll-like receptors\u2014redefining innate immunity","volume":"13","author":"O'Neill","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0244-x","article-title":"Molecular mechanisms and cellular functions of cGAS\u2013STING signalling","volume":"21","author":"Hopfner","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2630","article-title":"Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation","volume":"347","author":"Liu","year":"2015","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Regulation of type I interferon responses","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-\u03b2","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.041","article-title":"Toll-like receptors and the control of immunity","volume":"180","author":"Fitzgerald","year":"2020","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ncrna.2024.09.001","article-title":"Biological functions and affected signaling pathways by Long Non-Coding RNAs in the immune system","volume":"10","author":"Almanghadim","year":"2025","journal-title":"Non-coding RNA Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.7150\/thno.48520","article-title":"Roles of long non-coding RNAs and emerging RNA-binding proteins in innate antiviral responses","volume":"10","author":"Wang","year":"2020","journal-title":"Theranostics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41590-025-02355-9","article-title":"Long noncoding RNA regulation of immunity","volume":"27","author":"Yu","year":"2026","journal-title":"Nat Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055459","article-title":"Immunobiology of long noncoding RNAs","volume":"35","author":"Atianand","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2887","article-title":"Noncoding RNA and its associated proteins as regulatory elements of the immune system","volume":"15","author":"Turner","year":"2014","journal-title":"Nat Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2521","article-title":"Long non-coding RNAs: insights into functions","volume":"10","author":"Mercer","year":"2009","journal-title":"Nat Rev Genet"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2019.194419","article-title":"The how and why of lncRNA function: an innate immune perspective","volume":"1863","author":"Robinson","year":"2020","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"key":"B33","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1002\/JLB.3MIR0918-354R","article-title":"Long noncoding RNAs and the regulation of innate immunity and host-virus interactions","volume":"106","author":"Basavappa","year":"2019","journal-title":"J Leukoc Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.68","article-title":"Long noncoding RNAs in innate immunity","volume":"13","author":"Zhang","year":"2016","journal-title":"Cell Mol Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240925","article-title":"A long noncoding RNA mediates both activation and repression of immune response genes","volume":"341","author":"Carpenter","year":"2013","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-024-00749-3","article-title":"Decoding protein\u2013RNA interactions using CLIP-based methodologies","volume":"25","author":"Xiang","year":"2024","journal-title":"Nat Rev Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/ggn2.202500011","article-title":"Decoding RNA\u2013protein interactions: methodological advances and emerging challenges","volume":"6","author":"Yi","year":"2025","journal-title":"Adv Genet (Hoboken)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/asia.202500118","article-title":"Mapping RNA\u2013protein interactions via proximity labeling-based approaches","volume":"20","author":"Chen","year":"2025","journal-title":"Chem Asian J"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.29955","article-title":"EIF4A3 is stabilized by the long noncoding RNA BC200 to regulate gene expression during Epstein-Barr virus infection","volume":"96","author":"Li","year":"2024","journal-title":"J Med Virol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2025.110444","article-title":"Long noncoding RNA USP30-AS1 promotes influenza A virus replication by enhancing PHB1 function","volume":"303","author":"Yu","year":"2025","journal-title":"Vet Microbiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003932117","article-title":"LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity","volume":"117","author":"Liu","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00062-25","article-title":"LINC2781 enhances antiviral immunity against coxsackievirus B5 infection by activating the JAK-STAT pathway and blocking G3BP2-mediated STAT1 degradation","volume":"10","author":"Zhang","year":"2025","journal-title":"mSphere"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-023-09400-5","article-title":"Ubiquitin ligase enzymes and de-ubiquitinating enzymes regulate innate immunity in the TLR, NLR, RLR, and cGAS-STING pathways","volume":"71","author":"Jiang","year":"2023","journal-title":"Immunol Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/v13040584","article-title":"Negative regulation of the innate immune response through proteasomal degradation and deubiquitination","volume":"13","author":"Budroni","year":"2021","journal-title":"Viruses"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.503","article-title":"Mechanisms underlying ubiquitination","volume":"70","author":"Pickart","year":"2001","journal-title":"Annu Rev Biochem"},{"key":"B46","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nrm1552","article-title":"Proteolysis: from the lysosome to ubiquitin and the proteasome","volume":"6","author":"Ciechanover","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.012","article-title":"Ubiquitin: same molecule, different degradation pathways","volume":"143","author":"Clague","year":"2010","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1146\/annurev.biochem.78.101807.093809","article-title":"RING domain E3 ubiquitin ligases","volume":"78","author":"Deshaies","year":"2009","journal-title":"Annu Rev Biochem"},{"key":"B49","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.chom.2019.12.006","article-title":"lncRNA sensing of a viral suppressor of RNAi activates non-canonical innate immune signaling in Drosophila","volume":"27","author":"Zhang","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28637","article-title":"ZNFX1 antisense RNA1 promotes antiviral innate immune responses via modulating ZNFX1 function","volume":"95","author":"Jia","year":"2023","journal-title":"J Med Virol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11730","article-title":"Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing Tat protein degradation","volume":"7","author":"Li","year":"2016","journal-title":"Nat Commun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-021-00496-1","article-title":"Long non-coding RNA nuclear paraspeckle assembly transcript 1 promotes activation of T helper 2 cells via inhibiting STAT6 ubiquitination","volume":"34","author":"Huang","year":"2021","journal-title":"Hum Cell"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100856","article-title":"Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection","volume":"297","author":"Shen","year":"2021","journal-title":"J Biol Chem"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/cells13010071","article-title":"Viral targeting of Importin Alpha-mediated nuclear import to block innate immunity","volume":"13","author":"Vogel","year":"2024","journal-title":"Cells"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.15.1.607","article-title":"Transport between the cell nucleus and the cytoplasm","volume":"15","author":"G\u00f6rlich","year":"1999","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1080\/19491034.2024.2350182","article-title":"LncRNAs, nuclear architecture and the immune response","volume":"15","author":"Montano","year":"2024","journal-title":"Nucleus"},{"key":"B57","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1146\/annurev.cellbio.15.1.291","article-title":"Regulation of nuclear localization: a key to a door","volume":"15","author":"Kaffman","year":"1999","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-8-32","article-title":"Phosphorylation meets nuclear import: a review","volume":"8","author":"Nardozzi","year":"2010","journal-title":"Cell Commun Signal"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.10.014","article-title":"Nuclear import by karyopherin-\u03b2s: recognition and inhibition","volume":"1813","author":"Chook","year":"2011","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251456","article-title":"The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation","volume":"344","author":"Wang","year":"2014","journal-title":"Science"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109926","article-title":"IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation","volume":"37","author":"Xu","year":"2021","journal-title":"Cell Rep"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.5.2986","article-title":"Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation","volume":"18","author":"Lin","year":"1998","journal-title":"Mol Cell Biol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41467-025-55822-0","article-title":"lncRNA NORAD modulates STAT3\/STAT1 balance and innate immune responses in human cells via interaction with STAT3","volume":"16","author":"Argoetti","year":"2025","journal-title":"Nat Commun"},{"key":"B64","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.molcel.2014.01.009","article-title":"Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli","volume":"53","author":"Imamura","year":"2014","journal-title":"Mol Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1080\/19491034.2024.2350178","article-title":"Involvement of paraspeckle components in viral infections","volume":"15","author":"Milcamps","year":"2024","journal-title":"Nucleus"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113262","article-title":"Virus-induced lncRNA-BTX allows viral replication by regulating intracellular translocation of DHX9 and ILF3 to induce innate escape","volume":"42","author":"Cao","year":"2023","journal-title":"Cell Rep"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1126\/science.1115901","article-title":"A strategy for probing the function of noncoding RNAs finds a repressor of NFAT","volume":"309","author":"Willingham","year":"2005","journal-title":"Science"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00207-22","article-title":"The role of long noncoding RNA BST2-2 in the innate immune response to viral infection","volume":"96","author":"Chen","year":"2022","journal-title":"J Virol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041356","article-title":"Double-stranded RNA sensors and modulators in innate immunity","volume":"37","author":"Hur","year":"2019","journal-title":"Annu Rev Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13022","article-title":"The molecular mechanism of RIG-I activation and signaling","volume":"304","author":"Thoresen","year":"2021","journal-title":"Immunol Rev"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nature13140","article-title":"Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I","volume":"509","author":"Peisley","year":"2014","journal-title":"Nature"},{"key":"B72","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/j.1600-065X.2008.00727.x","article-title":"RNA recognition and signal transduction by RIG-I-like receptors","volume":"227","author":"Yoneyama","year":"2009","journal-title":"Immunol Rev"},{"key":"B73","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.cell.2018.03.064","article-title":"Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response","volume":"173","author":"Jiang","year":"2018","journal-title":"Cell"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00507-18","article-title":"Long noncoding RNA ITPRIP-1 positively regulates the innate immune response through promotion of oligomerization and activation of MDA5","volume":"92","author":"Xie","year":"2018","journal-title":"J Virol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160592","article-title":"TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity","volume":"214","author":"Lang","year":"2017","journal-title":"J Exp Med"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ai.2023.03.001","article-title":"RIG-I-like receptors: Molecular mechanism of activation and signaling","volume":"158","author":"Zheng","year":"2023","journal-title":"Adv Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.003","article-title":"Physiological functions of RIG-I-like receptors","volume":"57","author":"Yoneyama","year":"2024","journal-title":"Immunity"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.09.008","article-title":"The RIG-I-like receptor family of immune proteins","volume":"85","author":"van Huizen","year":"2025","journal-title":"Mol Cell"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.039","article-title":"Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA","volume":"147","author":"Kowalinski","year":"2011","journal-title":"Cell"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1842","article-title":"Post-translational modifications in signal integration","volume":"17","author":"Deribe","year":"2010","journal-title":"Nat Struct Mol Biol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/S0968-0004(00)01712-6","article-title":"The regulation of protein function by multisite phosphorylation\u2014a 25 year update","volume":"25","author":"Cohen","year":"2000","journal-title":"Trends Biochem Sci"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0379-0","article-title":"The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response","volume":"20","author":"Lin","year":"2019","journal-title":"Nat Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01296","article-title":"Recent advances and contradictions in the study of the individual roles of ubiquitin ligases that regulate RIG-I-like receptor-mediated antiviral innate immune responses","volume":"11","author":"Oshiumi","year":"2020","journal-title":"Front Immunol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1588","article-title":"TRIM25 and its emerging RNA-binding roles in antiviral defense","volume":"11","author":"Choudhury","year":"2020","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B85","doi-asserted-by":"publisher","first-page":"8485","DOI":"10.1038\/s41467-024-52918-x","article-title":"The molecular dissection of TRIM25\u2019s RNA-binding mechanism provides key insights into its antiviral activity","volume":"15","author":"\u00c1lvarez","year":"2024","journal-title":"Nat Commun"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104607","article-title":"LncNSPL facilitates influenza A viral immune escape by restricting TRIM25-mediated K63-linked RIG-I ubiquitination","volume":"25","author":"Jiang","year":"2022","journal-title":"iScience"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1016\/j.immuni.2020.11.010","article-title":"Decreased expression of the host long-noncoding RNA-GM facilitates viral escape by inhibiting the kinase activity TBK1 via S-glutathionylation","volume":"53","author":"Wang","year":"2020","journal-title":"Immunity"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0193-0","article-title":"Interferon-inducible cytoplasmic lncLrrc55-AS promotes antiviral innate responses by strengthening IRF3 phosphorylation","volume":"29","author":"Zhou","year":"2019","journal-title":"Cell Res"},{"key":"B89","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.virs.2023.08.001","article-title":"Long noncoding RNA 1392 regulates MDA5 by interaction with ELAVL1 to inhibit coxsackievirus B5 infection","volume":"38","author":"Li","year":"2023","journal-title":"Virol Sin"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.02.004","article-title":"A cytoplasmic NF-\u03baB-interacting long noncoding RNA blocks I\u03baB phosphorylation and suppresses breast cancer metastasis","volume":"27","author":"Liu","year":"2015","journal-title":"Cancer Cell"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00762","article-title":"A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics","volume":"2","author":"Rapicavoli","year":"2013","journal-title":"eLife"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525022113","article-title":"Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression","volume":"113","author":"Nishitsuji","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210321119","article-title":"Long noncoding RNA CHROMR regulates antiviral immunity in humans","volume":"119","author":"van Solingen","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5346.2075","article-title":"Signaling through scaffold, anchoring, and adaptor proteins","volume":"278","author":"Pawson","year":"1997","journal-title":"Science"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.634146","article-title":"RNAs as regulators of cellular matchmaking","volume":"8","author":"Fernandes","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142710","article-title":"Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits","volume":"75","author":"Bhattacharyya","year":"2006","journal-title":"Annu Rev Biochem"},{"key":"B97","doi-asserted-by":"publisher","first-page":"10224","DOI":"10.1038\/s41467-024-54674-4","article-title":"Promotion of TLR7-MyD88-dependent inflammation and autoimmunity in mice through stem-loop changes in Lnc-Atg16l1","volume":"15","author":"Yang","year":"2024","journal-title":"Nat Commun"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1038\/s41467-019-09482-6","article-title":"The lncRNA Neat1 promotes activation of inflammasomes in macrophages","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat Commun"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00791-2","article-title":"Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a","volume":"28","author":"Lai","year":"2021","journal-title":"Cell Death Differ"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01711","article-title":"A human long non-coding RNA LncATV promotes virus replication through restricting RIG-I-mediated innate immunity","volume":"10","author":"Fan","year":"2019","journal-title":"Front Immunol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1038\/s41467-017-02229-1","article-title":"The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation","volume":"8","author":"Du","year":"2017","journal-title":"Nat Commun"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.672165","article-title":"RDUR, a lncRNA, promotes innate antiviral responses and provides feedback control of NF-\u03baB activation","volume":"12","author":"Chen","year":"2021","journal-title":"Front Immunol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313768111","article-title":"The long noncoding RNA THRIL regulates TNF\u03b1 expression through its interaction with hnRNPL","volume":"111","author":"Li","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B104","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.molcel.2017.06.020","article-title":"HEXIM1 and NEAT1 long non-coding RNA form a multi-subunit complex that regulates DNA-mediated innate immune response","volume":"67","author":"Morchikh","year":"2017","journal-title":"Mol Cell"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920393117","article-title":"Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway","volume":"117","author":"Aznaourova","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"B106","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.coviro.2015.01.004","article-title":"RIG-I-like receptor regulation in virus infection and immunity","volume":"12","author":"Chan","year":"2015","journal-title":"Curr Opin Virol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0288-3","article-title":"RIG-I-like receptors: their regulation and roles in RNA sensing","volume":"20","author":"Rehwinkel","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1261\/rna.079016.121","article-title":"Cytoplasmic RNA sensors and their interplay with RNA-binding partners in innate antiviral response: theme and variations","volume":"28","author":"Chan","year":"2022","journal-title":"RNA"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.041","article-title":"MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response","volume":"146","author":"Hou","year":"2011","journal-title":"Cell"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3641","article-title":"The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination","volume":"18","author":"Liu","year":"2017","journal-title":"Nat Immunol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.7150\/thno.64880","article-title":"A novel lncRNA linc-AhRA negatively regulates innate antiviral response in murine microglia upon neurotropic herpesvirus infection","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"B112","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1038\/s41580-024-00748-6","article-title":"Identification of RNA structures and their roles in RNA functions","volume":"25","author":"Cao","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3390\/biom15060881","article-title":"LncRNA\u2013protein interactions: a key to deciphering lncRNA mechanisms","volume":"15","author":"Wang","year":"2025","journal-title":"Biomolecules"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220604","article-title":"A comprehensive review of methods to study lncRNA\u2013protein interactions in solution","volume":"50","author":"Badmalia","year":"2022","journal-title":"Biochem Soc Trans"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1841","article-title":"Stoichiometry of long noncoding RNA interactions with other RNAs: insights from OIP5-AS1","volume":"15","author":"Yang","year":"2024","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111870","article-title":"Nucleic acid\u2013protein condensates in innate immune signaling","volume":"42","author":"Corbet","year":"2023","journal-title":"EMBO J"},{"key":"B117","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s10555-024-10226-2","article-title":"TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond","volume":"44","author":"Wu","year":"2025","journal-title":"Cancer Metastasis Rev"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3580","article-title":"Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract","volume":"17","author":"Xing","year":"2016","journal-title":"Nat Immunol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/s41467-017-00101-w","article-title":"TRIM29 promotes DNA virus infections by inhibiting innate immune response","volume":"8","author":"Xing","year":"2017","journal-title":"Nat Commun"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701569","article-title":"TRIM29 negatively regulates the type I IFN production in response to RNA virus","volume":"201","author":"Xing","year":"2018","journal-title":"J Immunol"},{"key":"B121","doi-asserted-by":"publisher","first-page":"3481","DOI":"10.1038\/s41467-024-44745-x","article-title":"Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice","volume":"15","author":"Wang","year":"2024","journal-title":"Nat Commun"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2024.10.004","article-title":"TRIM29 controls enteric RNA virus-induced intestinal inflammation by targeting NLRP6 and NLRP9b signaling pathways","volume":"18","author":"Wang","year":"2025","journal-title":"Mucosal Immunol"},{"key":"B123","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.bsheal.2025.05.005","article-title":"lncRNA IPAN antagonizes RIG-I\/TRIM25-mediated degradation of influenza A virus PB1 to promote viral replication","volume":"7","author":"Sun","year":"2025","journal-title":"Biosaf Health"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2024.04.005","article-title":"Biochemical targets of the micropeptides encoded by lncRNAs","volume":"9","author":"Wang","year":"2024","journal-title":"Non-coding RNA Res"},{"key":"B125","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41420-024-02175-0","article-title":"Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications","volume":"10","author":"Xiao","year":"2024","journal-title":"Cell Death Discov"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.111112","article-title":"The long non-coding RNA MALAT1 encodes a micropeptide that promotes influenza A virus replication by suppressing innate immune responses","volume":"302","author":"Rai","year":"2026","journal-title":"J Biol Chem"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-024-00693-2","article-title":"Targeting and engineering long non-coding RNAs for cancer therapy","volume":"25","author":"Coan","year":"2024","journal-title":"Nat Rev Genet"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00662-1","article-title":"Non-coding RNAs in disease: from mechanisms to therapeutics","volume":"25","author":"Nemeth","year":"2024","journal-title":"Nat Rev Genet"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00219-z","article-title":"Noncoding RNA therapeutics\u2014challenges and potential solutions","volume":"20","author":"Winkle","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00912-9","article-title":"RNAi-based drug design: considerations and future directions","volume":"23","author":"Tang","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-024-03342-9","article-title":"Targeting RNA-protein interactions with small molecules: promise and therapeutic potential","volume":"33","author":"Rhodes","year":"2024","journal-title":"Med Chem Res"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-023-00569-9","article-title":"Small molecule approaches to targeting RNA","volume":"8","author":"Kovachka","year":"2024","journal-title":"Nat Rev Chem"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1298441","article-title":"Using the structural diversity of RNA: protein interfaces to selectively target RNA with small molecules in cells: methods and perspectives","volume":"10","author":"Li","year":"2023","journal-title":"Front Mol Biosci"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/nature17161","article-title":"Melanoma addiction to the long non-coding RNA SAMMSON","volume":"531","author":"Leucci","year":"2016","journal-title":"Nature"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2850","article-title":"The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells","volume":"73","author":"Gutschner","year":"2013","journal-title":"Cancer Res"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.12.011","article-title":"DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer","volume":"191","author":"Gofrit","year":"2014","journal-title":"J Urol"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-017-4293-0","article-title":"A phase 1\/2a, dose-escalation, safety, pharmacokinetic, and preliminary efficacy study of intraperitoneal administration of BC-819 (H19-DTA) in subjects with recurrent ovarian\/peritoneal cancer","volume":"295","author":"Lavie","year":"2017","journal-title":"Arch Gynecol Obstet"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.36.15_suppl.2557","article-title":"Phase 1 study of ANDES-1537: a novel antisense oligonucleotide against non-coding mitochondrial DNA in advanced solid tumors","volume":"36","author":"Dhawan","year":"2018","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1994058\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:36:45Z","timestamp":1791283005000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1994058\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":138,"alternative-id":["10.3389\/fimmu.2026.1994058"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1994058","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1994058"}}