Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L

https://m2.mtmt.hu/ hun 2026-04-15 01:20 JournalArticle 32039143 VALIDATED true Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI50484, R21DE019059, T32GM07229, T32DK07748, T32RR007063, R01NS029331, R42HL87688, R01CA044059]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA044059] Funding Source: NIH RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [T32RR007063] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R42HL087688] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI050484] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R21DE019059] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [T32DK007748] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM007229] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS029331] Funding Source: NIH RePORTER Funding text: National Institutes of Health (R01AI50484 and R21DE019059 to D.W.; T32GM07229, T32DK07748 and T32RR007063 to B.R.A.; R01NS029331 and R42HL87688 to K.K.; R01CA044059 to R.H.S). Funding for open access charge: National Institutes of Health (grant R42HL87688 to K.K.). Department of Medicine, University of Pennsylvania, 3610 Hamilton Walk, 522B Johnson Pavilion, Philadelphia, PA 19104, United States Department of Neurosurgery, 371 Stemmler Hall, University of Pennsylvania, Philadelphia, PA 19104, United States Department of Cancer Biology NB40, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States Cited By :99 Export Date: 28 May 2021 CODEN: NARHA Correspondence Address: Karikó, K.; Department of Neurosurgery, , Philadelphia, PA 19104, United States; email: kariko@mail.med.upenn.edu 0 false 2026-01-21T09:41:20.890+0000 2023-10-04T14:35:02.888+0000 2021-05-28T05:34:46.586+0000 true 10030409 Karikó Katalin /api/author/10030409 Author Karikó Katalin (biofizika) true 10030409 2024-02-20T09:26:36.465+0000 2021-06-01T07:34:38.411+0000 true 569 Balázs András /api/admin/569 Admin Balázs András (MTMT Központ_, admin) true Admin 10058227 /api/admin/10058227 Áts József (ÁtsJ adm2-3, admin) Áts József true 10058227 true 2023-11-06T07:04:02.893+0000 true false true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Szakcikk (Folyóiratcikk) 101 true 10000059 true 1 /api/category/1 Category Tudományos true 1 Anderson, Bart R. Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L true true /api/journal/3431 REVIEWED NUCLEIC ACIDS RESEARCH 0305-1048 1362-4962 true false 3431 false 3431 true 0305-1048 1362-4962 Journal FOREIGN 39 21 9329 9338 9329 10 2011 The interferon-induced enzymes 2'-5'-oligoadenylate synthetase (OAS) and RNase L are key components of innate immunity involved in sensory and effector functions following viral infections. Upon binding target RNA, OAS is activated to produce 2'-5'-linked oligoadenylates (2-5A) that activate RNase L, which then cleaves single-stranded self and non-self RNA. Modified nucleosides that are present in cellular transcripts have been shown to suppress activation of several RNA sensors. Here, we demonstrate that in vitro transcribed, unmodified RNA activates OAS, induces RNase L-mediated ribosomal RNA (rRNA) cleavage and is rapidly cleaved by RNase L. In contrast, RNA containing modified nucleosides activates OAS less efficiently and induces limited rRNA cleavage. Nucleoside modifications also make RNA resistant to cleavage by RNase L. Examining translation in RNase L-/- cells and mice confirmed that RNase L activity reduces translation of unmodified mRNA, which is not observed with modified mRNA. Additionally, mRNA containing the nucleoside modification pseudouridine is translated longer and has an extended half-life. The observation that modified nucleosides in RNA reduce 2-5A pathway activation joins OAS and RNase L to the list of RNA sensors and effectors whose functions are limited when RNA is modified, confirming the role of nucleoside modifications in suppressing immune recognition of RNA. 2021 true true true false false GOLD 2026-01-21 true https://doi.org/10.1093/nar/gkr586 268 0 268 247 5 265 265 257 228 268 268 247 247 247 21 0 268 247 268 247 0 4 4 Folyóiratcikk Journal Article 24 256 Könyvrészlet Chapter in Book 25 10 Könyv Book 23 2 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi 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PersonAuthorship 96437912 /api/authorship/96437912 Jha, Babal K. 3 0.16666667 false false false Jha Babal K. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 96437913 /api/authorship/96437913 Silverman, Robert H. 4 0.16666667 false false false Silverman Robert H. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 96437914 /api/authorship/96437914 Weissman, Drew 5 0.16666667 false false false Weissman Drew true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 96437915 /api/authorship/96437915 Kariko, Katalin ✉ [Karikó, Katalin (biofizika), szerző] 6 0.16666667 false true true Author 10030409 /api/author/10030409 Karikó Katalin (biofizika) Karikó Katalin true 10030409 true Kariko Katalin true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PublicationIdentifier 18844175 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(2011) NUCLEIC ACIDS RESEARCH 0305-1048 1362-4962 39 21 9329-9338<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Anderson Bart R. </span> ;    <span class="author-name" >Muramatsu Hiromi </span> ;    <span class="author-name" >Jha Babal K. </span> ;    <span class="author-name" >Silverman Robert H. </span> ;    <span class="author-name" >Weissman Drew </span> ;    <span class="author-name" mtid="10030409"><a href="/gui2/?type=authors&mode=browse&sel=10030409" target="_blank">Kariko Katalin ✉ (<span class="authorship-author-name">Karikó Katalin</span> <span class="authorAux-mtmt"> biofizika</span>) </a> </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32039143" target="_blank">Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L</a></div> <div> <span class="journal-title">NUCLEIC ACIDS RESEARCH</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0305-1048">0305-1048</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1362-4962">1362-4962</a>)</span>: <span class="journal-volume">39</span> <span class="journal-issue">21</span> <span class="page"> pp 9329-9338 </span> <span class="year">(2011)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1093/nar/gkr586" target="_blank" href="https://doi.org/10.1093/nar/gkr586"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000297375700030" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000297375700030"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="82255164455" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-82255164455"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="21813458" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=21813458&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Genetics   SJR indikátor: D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 268</span> | Független: 247 | Függő: 21 | Nem jelölt: 0 | WoS jelölt: 257 | Scopus jelölt: 228 | WoS/Scopus jelölt: 268 | DOI jelölt: 265 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32039143&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 4 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32039143</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">WOS TAGGED</span> </div> <div class="lastModified">Utolsó módosítás: 2023.10.04. 16:35 Bernátskyné Babus Csilla (SZTE admin4) </div> <div class="lockedBy">Központi kezelésű 2023.11.06. 08:04 Áts József (ÁtsJ adm2-3, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI50484, R21DE019059, T32GM07229, T32DK07748, T32RR007063, R01NS029331, R42HL87688, R01CA044059]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Ins...</pre> </div></div>