2026-09-17 マックス・プランク研究所
The non-coding RNA TRDN-AS plays an important role in maintaining a stable heart rhythm. It regulates the formation of various variants of the protein triadin and thereby influences calcium release in heart muscle cells. If TRDN-AS levels are reduced, this can disrupt calcium regulation and increase the risk of arrhythmias. © MPI for Heart and Lung Research
＜関連情報＞
- https://www.mpg.de/26983481/non-coding-rna-protects-the-heart-against-dangerous-arrhythmias
- https://www.nature.com/articles/s41467-026-75985-8
Trdn-asは、正確なトリアジンアイソフォームスイッチングのためにm6A依存性転写終結を誘導し、異常な二量体形成と心筋症を予防する Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy
Theresa Hofmann, Sara Hettrich, Bio Maria Ghéo Idrissou, Christian Waechter, Maria Weiss, Salma Hachim, Silke Kreher, Maximilian Staps, Laia Cañes Esteve, Sabine Pankuweit, Hendrik Milting, Mario Looso, Isabelle Marty, Stefan Engelhardt, Thomas Braun & Thomas Boettger
Nature Communications Published:25 July 2026
DOI:https://doi.org/10.1038/s41467-026-75985-8
Abstract
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.
