{"language":[{"iso":"eng"}],"external_id":{"pmid":["42635125"]},"volume":54,"date_published":"2026-09-09T00:00:00Z","type":"journal_article","intvolume":"        54","oa_version":"Published Version","quality_controlled":"1","file":[{"relation":"main_file","file_size":6016116,"date_created":"2026-09-09T11:29:49Z","access_level":"open_access","file_id":"22872","success":1,"file_name":"2026_NucleicAcidsResearch_Varada.pdf","date_updated":"2026-09-09T11:29:49Z","creator":"dernst","checksum":"319904a237f73dcc55daa4a56baa98fa","content_type":"application/pdf"}],"OA_type":"gold","ddc":["570"],"dataavailabilitystatement":"Sequencing data has been deposited at GEO and is available under accession number GSE293616.\r\nEditing analysis of protected dsRNA is available in GitHub, https://github.com/BioinfoUNIBA/Mouse-dsRNA-mda5, and Zenodo, https://doi.org/10.5281/zenodo.17876716.","month":"09","doi":"10.1093/nar/gkag845","pmid":1,"scopus_import":"1","department":[{"_id":"CaBe"},{"_id":"GradSch"}],"project":[{"grant_number":"F8003","name":"RNAdeco: decorating RNA for a purpose/ P03- Roles of A-to-I editing in dsRNA recognition","_id":"8dc144d4-16d5-11f0-9cad-9d9e86aea1f7"}],"OA_place":"publisher","status":"public","has_accepted_license":"1","article_type":"original","issue":"16","license":"https://creativecommons.org/licenses/by/4.0/","oa":1,"article_number":"gkag845","das_tickbox":"1","file_date_updated":"2026-09-09T11:29:49Z","supplementarymaterial":"yes","researchdata_availability":"yes","citation":{"chicago":"Varada, Rajagopal, Alina F. Leuchtenberger, Cornelia Vesely, Beata M Kaczmarek, Hamid Mansouri Khosravi, Therese C. Mandl, Katarina Milanovic, et al. “Distinguishing Self from Non-Self RNA by Editing-Specific Inosine Patterns.” <i>Nucleic Acids Research</i>. Oxford University Press, 2026. <a href=\"https://doi.org/10.1093/nar/gkag845\">https://doi.org/10.1093/nar/gkag845</a>.","short":"R. Varada, A.F. Leuchtenberger, C. Vesely, B.M. Kaczmarek, H. Mansouri Khosravi, T.C. Mandl, K. Milanovic, K. Honarmand Tamizkar, V. Rajendra, H. Senoner, L. Steinbichl, M. Borojevic, A. Sombke, K. Schmidt, M. Eckhard, I.L. Hofacker, C. Walkley, J.E. Heraud-Farlow, E. Picardi, C. Bernecky, M.F. Jantsch, Nucleic Acids Research 54 (2026).","ama":"Varada R, Leuchtenberger AF, Vesely C, et al. Distinguishing self from non-self RNA by editing-specific inosine patterns. <i>Nucleic Acids Research</i>. 2026;54(16). doi:<a href=\"https://doi.org/10.1093/nar/gkag845\">10.1093/nar/gkag845</a>","apa":"Varada, R., Leuchtenberger, A. F., Vesely, C., Kaczmarek, B. M., Mansouri Khosravi, H., Mandl, T. C., … Jantsch, M. F. (2026). Distinguishing self from non-self RNA by editing-specific inosine patterns. <i>Nucleic Acids Research</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/nar/gkag845\">https://doi.org/10.1093/nar/gkag845</a>","mla":"Varada, Rajagopal, et al. “Distinguishing Self from Non-Self RNA by Editing-Specific Inosine Patterns.” <i>Nucleic Acids Research</i>, vol. 54, no. 16, gkag845, Oxford University Press, 2026, doi:<a href=\"https://doi.org/10.1093/nar/gkag845\">10.1093/nar/gkag845</a>.","ista":"Varada R, Leuchtenberger AF, Vesely C, Kaczmarek BM, Mansouri Khosravi H, Mandl TC, Milanovic K, Honarmand Tamizkar K, Rajendra V, Senoner H, Steinbichl L, Borojevic M, Sombke A, Schmidt K, Eckhard M, Hofacker IL, Walkley C, Heraud-Farlow JE, Picardi E, Bernecky C, Jantsch MF. 2026. Distinguishing self from non-self RNA by editing-specific inosine patterns. Nucleic Acids Research. 54(16), gkag845.","ieee":"R. Varada <i>et al.</i>, “Distinguishing self from non-self RNA by editing-specific inosine patterns,” <i>Nucleic Acids Research</i>, vol. 54, no. 16. Oxford University Press, 2026."},"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"acknowledgement":"This work was supported by Austrian Science Fund project F80-07 to M.F.J., F80-03 to C.B., and ZK57-B28 to C.V.; National Health and Medical Research Council Australia (NHMRC; GNT2018098 to C.R.W.). The work was supported in part by the Victorian State Government Operational Infrastructure Support Scheme to St Vincent’s Institute and Hudson Institute of Medical Research. R.V. and A.L. were supported by Doc Fund/DOC32 of the Austrian Science Fund. Funding to pay the Open Access publication charges for this article was provided by Austrian Science Fund. For open access purposes, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission.","fulldoi":"https://doi.org/10.1093/nar/gkag845","date_created":"2026-08-30T22:01:44Z","DOAJ_listed":"1","publisher":"Oxford University Press","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2026-09-09T11:31:04Z","article_processing_charge":"Yes","day":"09","PlanS_conform":"1","publication_status":"published","_id":"22772","year":"2026","publication_identifier":{"eissn":["1362-4962"]},"author":[{"last_name":"Varada","full_name":"Varada, Rajagopal","first_name":"Rajagopal"},{"full_name":"Leuchtenberger, Alina F.","last_name":"Leuchtenberger","first_name":"Alina F."},{"first_name":"Cornelia","full_name":"Vesely, Cornelia","last_name":"Vesely"},{"first_name":"Beata M","id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","last_name":"Kaczmarek","full_name":"Kaczmarek, Beata M"},{"first_name":"Hamid","full_name":"Mansouri Khosravi, Hamid","last_name":"Mansouri Khosravi"},{"last_name":"Mandl","full_name":"Mandl, Therese C.","first_name":"Therese C."},{"first_name":"Katarina","full_name":"Milanovic, Katarina","last_name":"Milanovic"},{"last_name":"Honarmand Tamizkar","full_name":"Honarmand Tamizkar, Kasra","first_name":"Kasra"},{"full_name":"Rajendra, Vinod","last_name":"Rajendra","first_name":"Vinod"},{"full_name":"Senoner, Hannes","last_name":"Senoner","first_name":"Hannes"},{"last_name":"Steinbichl","full_name":"Steinbichl, Linda","first_name":"Linda"},{"last_name":"Borojevic","full_name":"Borojevic, Marija","first_name":"Marija"},{"full_name":"Sombke, Andy","last_name":"Sombke","first_name":"Andy"},{"first_name":"Katy","full_name":"Schmidt, Katy","last_name":"Schmidt"},{"full_name":"Eckhard, Margret","last_name":"Eckhard","first_name":"Margret"},{"last_name":"Hofacker","full_name":"Hofacker, Ivo L.","first_name":"Ivo L."},{"first_name":"Carl","full_name":"Walkley, Carl","last_name":"Walkley"},{"full_name":"Heraud-Farlow, Jacki E.","last_name":"Heraud-Farlow","first_name":"Jacki E."},{"full_name":"Picardi, Ernesto","last_name":"Picardi","first_name":"Ernesto"},{"orcid":"0000-0003-0893-7036","first_name":"Carrie A","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","full_name":"Bernecky, Carrie A","last_name":"Bernecky"},{"last_name":"Jantsch","full_name":"Jantsch, Michael F.","first_name":"Michael F."}],"publication":"Nucleic Acids Research","title":"Distinguishing self from non-self RNA by editing-specific inosine patterns","abstract":[{"lang":"eng","text":"The cytoplasmic antiviral sensor MDA5 is activated by double-stranded RNAs. Endogenous double-stranded RNAs are modified by the A-to-I RNA-editing ADAR family to prevent activation of MDA5. In vivo, cytoplasmic ADAR1p150 is critically required to suppress MDA5 activation, yet the editing signature of all ADAR isoforms is strongly overlapping in mice. Further, it is not clear how A-to-I modifications in dsRNA prevent MDA5 activation. Here we show that 3′ UTRs harboring inverted repeats activate MDA5 in vitro and in cells. In vitro editing by either ADAR isoform leads to editing at overlapping hotspot regions and prevents MDA5 activation in vitro and in cells. Remarkably, only inosines introduced by RNA editing are capable of suppressing MDA5 activation, while replacing guanosines with inosines during in vitro transcription has no impact on MDA5 activation. A comparison of inosines introduced by ADAR1p150 in vitro, in cells, and in vivo suggests that a small number of A-to-I conversions may be critically required to suppress MDA5 activation. As those critical editing events are predominantly altering A:U basepairs into I:U wobble basepairs, we suggest that the helical distortion introduced by those wobble pairs may prevent MDA5 polymerization and thus downstream activation of the type I interferon response."}]}