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SLM2 is a novel cardiac splicing factor involved in heart failure due to dilated cardiomyopathy

Alternative mRNA splicing is a fundamental process to increase the versatility of the genome. In humans, cardiac mRNA splicing is involved in the pathophysiology of heart failure. Mutations in the splicing factor RNA binding motif protein 20 (RBM20) cause severe forms of cardiomyopathy. To identify...

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Main Authors: Boeckel, Jes-Niels (Author) , Möbius-Winkler, Maximilian Nicolas Werner (Author) , Müller, Marion (Author) , Rebs, Sabine (Author) , Eger, Nicole (Author) , Schoppe, Laura (Author) , Tappu, Rewati (Author) , Kokot, Karoline E. (Author) , Kneuer, Jasmin Marga (Author) , Gaul, Susanne (Author) , Bordalo, Diana M. (Author) , Lai, Alan (Author) , Haas, Jan (Author) , Ghanbari, Mahsa (Author) , Drewe-Boss, Philipp (Author) , Liss, Martin (Author) , Katus, Hugo (Author) , Ohler, Uwe (Author) , Gotthardt, Michael (Author) , Laufs, Ulrich (Author) , Streckfuss-Bömeke, Katrin (Author) , Meder, Benjamin (Author)
Format: Article (Journal)
Language:English
Published: 15 July 2021
In: Genomics, proteomics & bioinformatics
Year: 2022, Volume: 20, Issue: 1, Pages: 129-146
ISSN:2210-3244
DOI:10.1016/j.gpb.2021.01.006
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.gpb.2021.01.006
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1672022921001467
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Author Notes:Jes-Niels Boeckel, Maximilian Möbius-Winkler, Marion Müller, Sabine Rebs, Nicole Eger, Laura Schoppe, Rewati Tappu, Karoline E. Kokot, Jasmin M. Kneuer, Susanne Gaul, Diana M. Bordalo, Alan Lai, Jan Haas, Mahsa Ghanbari, Philipp Drewe-Boss, Martin Liss, Hugo A. Katus, Uwe Ohler, Michael Gotthardt, Ulrich Laufs, Katrin Streckfuss-Bömeke, Benjamin Meder
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Summary:Alternative mRNA splicing is a fundamental process to increase the versatility of the genome. In humans, cardiac mRNA splicing is involved in the pathophysiology of heart failure. Mutations in the splicing factor RNA binding motif protein 20 (RBM20) cause severe forms of cardiomyopathy. To identify novel cardiomyopathy-associated splicing factors, RNA-seq and tissue-enrichment analyses were performed, which identified up-regulated expression of Sam68-Like mammalian protein 2 (SLM2) in the left ventricle of dilated cardiomyopathy (DCM) patients. In the human heart, SLM2 binds to important transcripts of sarcomere constituents, such as those encoding myosin light chain 2 (MYL2), troponin I3 (TNNI3), troponin T2 (TNNT2), tropomyosin 1/2 (TPM1/2), and titin (TTN). Mechanistically, SLM2 mediates intron retention, prevents exon exclusion, and thereby mediates alternative splicing of the mRNA regions encoding the variable proline-, glutamate-, valine-, and lysine-rich (PEVK) domain and another part of the I-band region of titin. In summary, SLM2 is a novel cardiac splicing regulator with essential functions for maintaining cardiomyocyte integrity by binding to and processing the mRNAs of essential cardiac constituents such as titin.
Item Description:Gesehen am 13.12.2022
Physical Description:Online Resource
ISSN:2210-3244
DOI:10.1016/j.gpb.2021.01.006

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