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| Item Type: | Article |
|---|---|
| Title: | Loss of cardiac splicing regulator RBM20 is associated with early-onset atrial fibrillation |
| Creators Name: | Vad, O.B. and Angeli, E. and Liss, M. and Ahlberg, G. and Andreasen, L. and Christophersen, I.E. and Hansen, C.C. and Møller, S. and Hellsten, Y. and Haunsoe, S. and Tveit, A. and Svendsen, J.H. and Gotthardt, M. and Lundegaard, P.R. and Olesen, M.S. |
| Abstract: | We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria. |
| Keywords: | Alternative Splicing, Atrial Cardiomyopathy, Atrial Fibrillation, Genetics, RBM20, Animals, Rats |
| Source: | JACC: Basic to Translational Science |
| ISSN: | 2452-302X |
| Publisher: | American College of Cardiology |
| Volume: | 9 |
| Number: | 2 |
| Page Range: | 163-180 |
| Date: | February 2024 |
| Official Publication: | https://doi.org/10.1016/j.jacbts.2023.08.008 |
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