https://m2.mtmt.hu/ hun 2026-03-12 12:01 true true 1 4 4 1 100 1 4 DESC publishedYear false ASC firstAuthor true ASC title true JournalArticle 32039148 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, R42HL87688, R01GM058709]; 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, R01GM058709] Funding Source: NIH RePORTER Funding text: The National Institutes of Health (R01AI50484, R21DE019059 to D.W., T32GM07229, T32DK07748, T32RR007063 to B.R.A., R42HL87688 to K.K. and R01GM058709 to P.C.B.). Funding for open access charge: National Institutes of Health grant R42HL87688. Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States Department of Chemistry, Pennsylvania State University, University Park, PA, United States Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States Cited By :156 Export Date: 28 May 2021 CODEN: NARHA Correspondence Address: Karikó, K.; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States; email: kariko@mail.med.upenn.edu 0 false 2026-02-17T18:32:04.755+0000 2023-10-04T14:35:06.721+0000 2021-05-28T05:35:28.224+0000 true 10030409 Karikó Katalin /api/author/10030409 Author true 10030409 2024-02-20T09:28:27.156+0000 2021-06-01T07:39:49.817+0000 true 569 Balázs András /api/admin/569 Admin true Admin 10058227 /api/admin/10058227 Áts József true 10058227 true 2023-11-06T07:03:54.778+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Anderson, Bart R. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation true true /api/journal/3431 REVIEWED true false 3431 false 3431 true 0305-1048 1362-4962 Journal FOREIGN 38 17 5884 5892 5884 9 2010 Previous studies have shown that the translation level of in vitro transcribed messenger RNA (mRNA) is enhanced when its uridines are replaced with pseudouridines; however, the reason for this enhancement has not been identified. Here, we demonstrate that in vitro transcripts containing uridine activate RNA-dependent protein kinase (PKR), which then phosphorylates translation initiation factor 2-alpha (eIF-2 alpha), and inhibits translation. In contrast, in vitro transcribed mRNAs containing pseudouridine activate PKR to a lesser degree, and translation of pseudouridine-containing mRNAs is not repressed. RNA pull-down assays demonstrate that mRNA containing uridine is bound by PKR more efficiently than mRNA with pseudouridine. Finally, the role of PKR is validated by showing that pseudouridine- and uridine-containing RNAs were translated equally in PKR knockout cells. These results indicate that the enhanced translation of mRNAs containing pseudouridine, compared to those containing uridine, is mediated by decreased activation of PKR. 2021 true true true false false GOLD 2026-02-17 true https://doi.org/10.1093/nar/gkq347 538 1 538 513 6 533 531 518 409 538 538 513 513 513 25 0 538 513 538 513 0 4 4 D1 false false false false 2021-08-26T05:43:55.233+0000 1 6 0 7 0 true 10058227 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 96437975 /api/authorship/96437975 1 0.14285715 true false false Anderson Bart R. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437976 /api/authorship/96437976 2 0.14285715 false false false Muramatsu Hiromi true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437977 /api/authorship/96437977 3 0.14285715 false false false Nallagatla Subba R. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437978 /api/authorship/96437978 4 0.14285715 false false false Bevilacqua Philip C. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437979 /api/authorship/96437979 5 0.14285715 false false false Sansing Lauren H. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437980 /api/authorship/96437980 6 0.14285715 false false false Weissman Drew true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437981 /api/authorship/96437981 7 0.14285715 false true true Author 10030409 /api/author/10030409 Karikó Katalin true 10030409 true Kariko Katalin true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 18844190 /api/publicationidentifier/18844190 PlainSource 6 /api/publicationsource/6 PublicationSourceType 10001 /api/publicationsourcetype/10001 true true true DOI DOI https://doi.org/@@@ true true 6 true GOLD true IDENTICAL 10.1093/nar/gkq347 https://doi.org/10.1093/nar/gkq347 false true PublicationIdentifier 18844191 /api/publicationidentifier/18844191 PlainSource 1 /api/publicationsource/1 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 000282173300028 https://www.webofscience.com/wos/woscc/full-record/000282173300028 false true PublicationIdentifier 18844233 /api/publicationidentifier/18844233 PlainSource 3 /api/publicationsource/3 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 77957242130 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-77957242130 false true PublicationIdentifier 18844192 /api/publicationidentifier/18844192 PlainSource 17 /api/publicationsource/17 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 20457754 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20457754&dopt=Abstract false true Keyword 231 /api/keyword/231 true 231 true Keyword 3076 /api/keyword/3076 true 3076 true Keyword 1000547 /api/keyword/1000547 true 1000547 true Keyword 1007241 /api/keyword/1007241 true 1007241 true Keyword 1071270 /api/keyword/1071270 true 1071270 true Keyword 1789435 /api/keyword/1789435 true true Keyword 2177821 /api/keyword/2177821 true true Keyword 2315353 /api/keyword/2315353 true true Keyword 2315355 /api/keyword/2315355 true true SjrRating 5740363 /api/sjrrating/5740363 17 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 1311 /api/classificationexternal/1311 true 1311 true D1 DIRECT true 5740363 true /api/publication/32039148 <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> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Muramatsu Hiromi </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Nallagatla Subba R. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Bevilacqua Philip C. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Sansing Lauren H. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Weissman Drew </span> ;&nbsp;&nbsp;&nbsp; <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;32039148" target="_blank">Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation</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">38</span> <span class="journal-issue">17</span> <span class="page"> pp 5884-5892 </span> <span class="year">(2010)</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/gkq347" target="_blank" href="https://doi.org/10.1093/nar/gkq347"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000282173300028" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000282173300028"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="77957242130" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-77957242130"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="20457754" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20457754&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Genetics&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;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: 538</span> | Független: 513 | Függő: 25 | Nem jelölt: 0 | WoS jelölt: 518 | Scopus jelölt:&nbsp;409 | WoS/Scopus jelölt:&nbsp;538 | DOI jelölt:&nbsp;531 (Nem nyilvános:&nbsp;1) </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32039148&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 4 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32039148</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. 08:03 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, R42HL87688, R01GM058709]; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for...</pre> </div></div> JournalArticle 32039151 VALIDATED true Funding Agency and Grant Number: National Institutes of Health (NIH) [NIAID AI-050484, NHLBI HL87688, NINDS NS-29331]; Ruth L. Kirschstein National Research Service Awards Funding text: This work was supported by the National Institutes of Health (NIH) grants NIAID AI-050484, NHLBI HL87688, and NINDS NS-29331. H. M. was supported by Ruth L. Kirschstein National Research Service Awards postdoctoral fellowship. We thank Houping Ni for technical assistance. K. K. and D. W. have formed a small biotech company that receives funding from the NIH to explore the use of nucleoside-modified mRNA for gene therapy. 0 false 2026-03-09T14:02:57.529+0000 2023-10-04T14:34:04.667+0000 2021-05-28T05:35:35.443+0000 true 10030409 Karikó Katalin /api/author/10030409 Author true 10030409 2024-02-20T09:30:40.088+0000 2021-06-01T08:33:27.607+0000 true 569 Balázs András /api/admin/569 Admin true Admin 10058227 /api/admin/10058227 Áts József true 10058227 true 2023-11-06T07:03:50.271+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Kariko, Katalin Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability true true /api/journal/30657 REVIEWED true false 30657 false 30657 true 1525-0016 1525-0024 Journal FOREIGN 16 11 1833 1840 1833 8 2008 In vitro-transcribed mRNAs encoding physiologically important proteins have considerable potential for therapeutic applications. However, in its present form, mRNA is unfeasible for clinical use because of its labile and immunogenic nature. Here, we investigated whether incorporation of naturally modified nucleotides into transcripts would confer enhanced biological properties to mRNA. We found that mRNAs containing pseudouridines have a higher translational capacity than unmodified mRNAs when tested in mammalian cells and lysates or administered intravenously into mice at 0.015-0.15 mg/kg doses. The delivered mRNA and the encoded protein could be detected in the spleen at 1, 4, and 24 hours after the injection, where both products were at significantly higher levels when pseudouridine-containing mRNA was administered. Even at higher doses, only the unmodified mRNA was immunogenic, inducing high serum levels of interferon-alpha ( IFN-alpha). These findings indicate that nucleoside modification is an effective approach to enhance stability and translational capacity of mRNA while diminishing its immunogenicity in vivo. Improved properties conferred by pseudouridine make such mRNA a promising tool for both gene replacement and vaccination. 2021 true true true false false NONE 2026-03-09 false 1439 7 1439 1374 13 1425 1424 1382 1095 1439 1439 1374 1374 1374 65 0 1439 1374 1439 1374 0 3 3 D1 false 10030409 false false false 2021-08-26T05:44:18.897+0000 1 6 0 7 0 true 10058227 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 96437995 /api/authorship/96437995 1 0.14285715 true false true Author 10030409 /api/author/10030409 Karikó Katalin true 10030409 true Kariko Katalin true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437996 /api/authorship/96437996 2 0.14285715 false false false Muramatsu Hiromi true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437997 /api/authorship/96437997 3 0.14285715 false false false Welsh Frank A. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437998 /api/authorship/96437998 4 0.14285715 false false false Ludwig Janos true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96437999 /api/authorship/96437999 5 0.14285715 false false false Kato Hiroki true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96438000 /api/authorship/96438000 6 0.14285715 false false false Akira Shizuo true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96438001 /api/authorship/96438001 7 0.14285715 false true false Weissman Drew true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 18844196 /api/publicationidentifier/18844196 PlainSource 6 /api/publicationsource/6 PublicationSourceType 10001 /api/publicationsourcetype/10001 true true true DOI DOI https://doi.org/@@@ true true 6 true IDENTICAL 10.1038/mt.2008.200 https://doi.org/10.1038/mt.2008.200 false true PublicationIdentifier 18844197 /api/publicationidentifier/18844197 PlainSource 1 /api/publicationsource/1 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 000260472600013 https://www.webofscience.com/wos/woscc/full-record/000260472600013 false true PublicationIdentifier 18844234 /api/publicationidentifier/18844234 PlainSource 3 /api/publicationsource/3 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 54949112814 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-54949112814 false true PublicationIdentifier 18844198 /api/publicationidentifier/18844198 PlainSource 17 /api/publicationsource/17 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 18797453 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=18797453&dopt=Abstract false true Keyword 621 /api/keyword/621 true 621 true Keyword 1662 /api/keyword/1662 true 1662 true Keyword 1679 /api/keyword/1679 true 1679 true Keyword 4591 /api/keyword/4591 true 4591 true Keyword 1000547 /api/keyword/1000547 true 1000547 true Keyword 1003555 /api/keyword/1003555 true 1003555 true Keyword 1071408 /api/keyword/1071408 true 1071408 true Keyword 1083287 /api/keyword/1083287 true 1083287 true Keyword 1321732 /api/keyword/1321732 true 1321732 true Keyword 1494834 /api/keyword/1494834 true true Keyword 1494914 /api/keyword/1494914 true true SjrRating 5858593 /api/sjrrating/5858593 4 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 3002 /api/classificationexternal/3002 true 3002 true D1 DIRECT true 5858593 true /api/publication/32039151 <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" 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> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Muramatsu Hiromi </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Welsh Frank A. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ludwig Janos </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kato Hiroki </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Akira Shizuo </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Weissman Drew </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32039151" target="_blank">Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability</a></div> <div> <span class="journal-title">MOLECULAR THERAPY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1525-0016">1525-0016</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1525-0024">1525-0024</a>)</span>: <span class="journal-volume">16</span> <span class="journal-issue">11</span> <span class="page"> pp 1833-1840 </span> <span class="year">(2008)</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_none" title="none"> <a style="color:blue" title="10.1038/mt.2008.200" target="_blank" href="https://doi.org/10.1038/mt.2008.200"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000260472600013" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000260472600013"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="54949112814" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-54949112814"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="18797453" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=18797453&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Drug Discovery&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Medicine&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Pharmacology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Genetics&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</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: 1,439</span> | Független: 1,374 | Függő: 65 | Nem jelölt: 0 | WoS jelölt: 1,382 | Scopus jelölt:&nbsp;1,095 | WoS/Scopus jelölt:&nbsp;1,439 | DOI jelölt:&nbsp;1,424 (Nem nyilvános:&nbsp;7) </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32039151&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 3 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32039151</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. 16:34 Bernátskyné Babus Csilla (SZTE admin4) </div> <div class="lockedBy">Központi kezelésű 2023.11.06. 08:03 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 Health (NIH) [NIAID AI-050484, NHLBI HL87688, NINDS NS-29331]; Ruth L. Kirschstein National Research Service Awards Funding text: This work was supported by the National Institutes of Health (NIH) grants NIAID AI-050484, NHLBI HL87688, and NINDS NS-29331. H. M. was supported by Ruth L. Kirschstein National Research Service Awar...</pre> </div></div> JournalArticle 32039262 VALIDATED true 0 false 2026-03-05T08:42:06.597+0000 2023-10-03T21:12:40.662+0000 2021-05-28T06:30:28.573+0000 true 10030409 Karikó Katalin /api/author/10030409 Author true 10030409 2023-10-03T21:12:24.789+0000 2023-10-03T21:12:24.789+0000 2023-10-03T21:12:41.034+0000 true 10018695 Bernátskyné Babus Csilla /api/admin/10018695 Admin true 10018695 Admin 10058227 /api/admin/10058227 Áts József true 10058227 true 2023-11-06T07:03:32.498+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Karikó, K. Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA true true /api/journal/1915 REVIEWED true false 1915 false 1915 true 1074-7613 1097-4180 Journal FOREIGN 23 2 165 175 165 11 2005 DNA and RNA stimulate the mammalian innate immune system through activation of Toll-like receptors (TLRs). DNA containing methylated CpG motifs, however, is not stimulatory. Selected nucleosides in naturally occurring RNA are also methylated or otherwise modified, but the immunomodulatory effects of these alterations remain untested. We show that RNA signals through human TLR3, TLR7, and TLR8, but incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine ablates activity. Dendritic cells (DCs) exposed to such modified RNA express significantly less cytokines and activation markers than those treated with unmodified RNA. DCs and TLR-expressing cells are potently activated by bacterial and mitochondrial RNA, but not by mammalian total RNA, which is abundant in modified nucleosides. We conclude that nucleoside modifications suppress the potential of RNA to activate DCs. The innate immune system may therefore detect RNA lacking nucleoside modification as a means of selectively responding to bacteria or necrotic tissue. Copyright ©2005 by Elsevier Inc. 2021 true true true false false NONE 2026-03-05 false 2032 9 2031 1972 13 2021 2004 1945 1589 2032 2031 1973 1972 1973 59 0 2032 1973 2031 1972 0 4 4 D1 true 10030409 false false false 2021-08-26T08:08:07.423+0000 1 6 0 4 0 true 10058227 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 96439159 /api/authorship/96439159 1 0.25 true false true Author 10030409 /api/author/10030409 Karikó Katalin true 10030409 true Karikó K. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96439160 /api/authorship/96439160 2 0.25 false false false Buckstein M. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96439161 /api/authorship/96439161 3 0.25 false false false Ni H. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96439162 /api/authorship/96439162 4 0.25 false true false Weissman D. true false 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Katalin</span> <span class="authorAux-mtmt"> biofizika</span>) </a> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Buckstein M. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ni H. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Weissman D. </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32039262" target="_blank">Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA</a></div> <div> <span class="journal-title">IMMUNITY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1074-7613">1074-7613</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1097-4180">1097-4180</a>)</span>: <span class="journal-volume">23</span> <span class="journal-issue">2</span> <span class="page"> pp 165-175 </span> <span class="year">(2005)</span> </div> <div class="pub-footer"> <span class="language" 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class="journal-subject">Folyóirat szakterülete: Scopus - Immunology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Immunology and Allergy&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Infectious Diseases&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;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: 2,032</span> | Független: 1,973 | Függő: 59 | Nem jelölt: 0 | WoS jelölt: 1,945 | Scopus jelölt:&nbsp;1,589 | WoS/Scopus jelölt:&nbsp;2,032 | DOI jelölt:&nbsp;2,004 (Nem nyilvános:&nbsp;9) </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32039262&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 4 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32039262</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">Scopus</span> </div> <div class="lastModified">Utolsó módosítás: 2023.10.03. 23:12 Bernátskyné Babus Csilla (SZTE admin4) </div> <div class="lockedBy">Központi kezelésű 2023.11.06. 08:03 Áts József (ÁtsJ adm2-3, admin) </div> </div></div> JournalArticle 32039266 VALIDATED true 0 false 2026-03-08T11:32:24.848+0000 2023-10-03T21:19:30.764+0000 2021-05-28T06:30:48.610+0000 true 10030409 Karikó Katalin /api/author/10030409 Author true 10030409 2023-10-03T21:19:21.921+0000 2023-10-03T21:19:21.921+0000 2023-10-03T21:19:31.163+0000 true 10018695 Bernátskyné Babus Csilla /api/admin/10018695 Admin true 10018695 Admin 10058227 /api/admin/10058227 Áts József true 10058227 true 2023-11-06T07:03:17.841+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Karikó, K. mRNA Is an Endogenous Ligand for Toll-like Receptor 3 true true /api/journal/2295 REVIEWED true false 2295 false 2295 true 0021-9258 1083-351X Journal FOREIGN 279 13 12542 12550 12542 9 2004 Toll-like receptors (TLRs) are the basic signaling receptors of the innate immune system. They are activated by molecules associated with pathogens or injured host cells and tissue. TLR3 has been shown to respond to double stranded (ds) RNA, a replication intermediary for many viruses. Here we present evidence that heterologous RNA released from or associated with necrotic cells or generated by in vitro transcription also stimulates TLR3 and induces immune activation. To assess RNA-mediated TLR3 activation, human embryonic kidney 293 cells stably expressing TLR3 and containing a nuclear factor-κB-dependent luciferase reporter were generated. Exposing these cells to in vitro transcribed RNA resulted in a TLR3-dependent induction of luciferase activity and interleukin-8 secretion. Treatment with in vitro transcribed mRNA activated nuclear factor-κB via TLR3 through a process that was dose-dependent and involved tyrosine phosphorylation. Furthermore, in vitro transcribed natural or 2′-fluoro-substituted mRNA induced the expression of TLR3, interferon regulatory factor-1, tumor necrosis factor-α, and interleukin-1 receptor-associated kinase-M mRNA in human dendritic cells (DCs). DCs responded to mRNA treatment by expressing activation markers, and this maturation was inhibited by antagonistic TLR3-specific antibody. Endogenous RNA released from or associated with necrotic cells also stimulated DCs, leading to interferon-α secretion, which could be abolished by pretreatment of necrotic cells with RNase. These results demonstrate that RNA, likely through secondary structure, is a potent host-derived activator of TLR3. This finding has potential physiologic relevance because RNA escaping from damaged tissue or contained within endocytosed cells could serve as an endogenous ligand for TLR3 that induces or otherwise modulates immune responses. 2021 true true true false false NONE 2026-03-08 false 983 1 983 971 4 978 946 934 896 982 982 970 970 971 12 0 983 971 983 971 0 3 3 D1 false 10030409 false false false 2021-08-26T08:08:11.230+0000 1 6 0 5 0 true 10058227 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 96439177 /api/authorship/96439177 1 0.2 true false true Author 10030409 /api/author/10030409 Karikó Katalin true 10030409 true Karikó K. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96439178 /api/authorship/96439178 2 0.2 false false false Ni H. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96439179 /api/authorship/96439179 3 0.2 false false false Capodici J. true 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/api/keyword/1147713 true 1147713 true Keyword 1512894 /api/keyword/1512894 true true Keyword 1515540 /api/keyword/1515540 true true Keyword 1693625 /api/keyword/1693625 true true Keyword 1796663 /api/keyword/1796663 true true SjrRating 5988745 /api/sjrrating/5988745 8 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 1303 /api/classificationexternal/1303 true 1303 true D1 DIRECT true 5988745 true /api/publication/32039266 <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" mtid="10030409"><a href="/gui2/?type=authors&mode=browse&sel=10030409" target="_blank">Karikó K. ✉ (<span class="authorship-author-name">Karikó Katalin</span> <span class="authorAux-mtmt"> biofizika</span>) </a> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ni H. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Capodici J. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Lamphier M. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Weissman D. </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32039266" target="_blank">mRNA Is an Endogenous Ligand for Toll-like Receptor 3</a></div> <div> <span class="journal-title">JOURNAL OF BIOLOGICAL CHEMISTRY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0021-9258">0021-9258</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1083-351X">1083-351X</a>)</span>: <span class="journal-volume">279</span> <span class="journal-issue">13</span> <span class="page"> pp 12542-12550 </span> <span class="year">(2004)</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_none" title="none"> <a style="color:blue" title="10.1074/jbc.M310175200" target="_blank" href="https://doi.org/10.1074/jbc.M310175200"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000220334900066" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000220334900066"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="1842477469" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-1842477469"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="14729660" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14729660&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Biochemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cell Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;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: 983</span> | Független: 971 | Függő: 12 | Nem jelölt: 0 | WoS jelölt: 934 | Scopus jelölt:&nbsp;896 | WoS/Scopus jelölt:&nbsp;982 | DOI jelölt:&nbsp;946 (Nem nyilvános:&nbsp;1) </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32039266&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 3 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32039266</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">Scopus</span> </div> <div class="lastModified">Utolsó módosítás: 2023.10.03. 23:19 Bernátskyné Babus Csilla (SZTE admin4) </div> <div class="lockedBy">Központi kezelésű 2023.11.06. 08:03 Áts József (ÁtsJ adm2-3, admin) </div> </div></div>