Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy.
T, H., S, H., BMG, I., C, W., M, W., S, H., S, K., M, S., L, C.E., & S, P. (2026). Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy.. Nature communications. https://doi.org/10.1038/s41467-026-75985-8
T H, S H, BMG I, C W, M W, S H, et al. Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy.. Nature communications. 2026; doi: 10.1038/s41467-026-75985-8
T H, S H, BMG I, et al. Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy.[J]. Nature communications. 2026. DOI: 10.1038/s41467-026-75985-8.
@article{t2026,
author = {Hofmann T and Hettrich S and Idrissou BMG and Waechter C and Weiss M and Hachim S and Kreher S and Staps M and Cañes Esteve L and Pankuweit S},
title = {Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy.},
journal = {Nature communications},
year = {2026},
doi = {10.1038/s41467-026-75985-8},
note = {PMID: 42502078},
}
TY - JOUR AU - Hofmann T AU - Hettrich S AU - Idrissou BMG AU - Waechter C AU - Weiss M AU - Hachim S AU - Kreher S AU - Staps M AU - Cañes Esteve L AU - Pankuweit S TI - Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy. T2 - Nature communications PY - 2026 DO - 10.1038/s41467-026-75985-8 AN - PMID:42502078 ER -
Heart failure is a leading cause of mortality, and impaired cardiac excitation-contraction coupling represents a potentially fatal trigger for myocardial dysfunction. Long non-coding RNAs (lncRNAs) can contribute to cardiomyopathy, but comprehensive mechanistic insights remain elusive. We demonstrate that reduction of the lncRNA TRDN-AS in human cardiomyopathy or abrogating it in human iPSC-derived cardiomyocytes and mice causes a switch of cardiac TRDN/TRISK32 to skeletal muscle TRDN/TRISK95. Transcription of Trdn-as in cis is essential for stalling RNA Pol II at the 3' end of the cardiac Trdn 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 Trdn 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.