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Long non-coding RNAs (lncRNAs) can contribute to cardiomyopathy, but comprehensive mechanistic insights remain elusive. We demonstrate that reduction of the lncRNA\n                    <jats:italic>TRDN-AS<\/jats:italic>\n                    in human cardiomyopathy or abrogating it in human iPSC-derived cardiomyocytes and mice causes a switch of cardiac TRDN\/TRISK32 to skeletal muscle\u00a0TRDN\/TRISK95. Transcription of\n                    <jats:italic>Trdn-as<\/jats:italic>\n                    in\n                    <jats:italic>cis<\/jats:italic>\n                    is essential for stalling RNA Pol II at the 3\u2019 end of the cardiac\n                    <jats:italic>Trdn<\/jats:italic>\n                    transcript, promoting the formation of the cardiac TRDN\/TRISK32 isoform. The m6A-methyltransferase METTL3 is crucial for RNA Pol II stalling, enforcing transcriptional termination and proximal polyadenylation of the\n                    <jats:italic>Trdn<\/jats:italic>\n                    transcript. Here, we establish that the switch of TRDN isoforms results in a significantly altered interactome of the cardiac calcium release complex, aberrant calcium handling, altered dyad structure, QT prolongation, and dilated cardiomyopathy in mice and humans.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-75985-8","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T07:34:15Z","timestamp":1784964855000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy"],"prefix":"10.1038","volume":"17","author":[{"given":"Theresa","family":"Hofmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8355-3349","authenticated-orcid":false,"given":"Sara","family":"Hettrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4650-2511","authenticated-orcid":false,"given":"Bio Maria Gh\u00e9o","family":"Idrissou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-0696","authenticated-orcid":false,"given":"Christian","family":"Waechter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Hachim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0890-2979","authenticated-orcid":false,"given":"Silke","family":"Kreher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7294-4563","authenticated-orcid":false,"given":"Maximilian","family":"Staps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-1321","authenticated-orcid":false,"given":"Laia","family":"Ca\u00f1es Esteve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Pankuweit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Milting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1495-9530","authenticated-orcid":false,"given":"Mario","family":"Looso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-913X","authenticated-orcid":false,"given":"Isabelle","family":"Marty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5378-8661","authenticated-orcid":false,"given":"Stefan","family":"Engelhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-4804","authenticated-orcid":false,"given":"Thomas","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4280-8449","authenticated-orcid":false,"given":"Thomas","family":"Boettger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"75985_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/BF01774031","volume":"12","author":"E Rios","year":"1991","unstructured":"Rios, E., Ma, J. 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