SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy
| Autor: | Michael Gotthardt, Jes-Niels Boeckel, Mahsa Ghanbari, Maximilian Möbius-Winkler, Martin Liss, Jasmin M Kneuer, Uwe Ohler, Philipp Drewe-Boss, Sabine Rebs, Alan Lai, Katrin Streckfuss-Bömeke, Nicole Eger, Karoline E. Kokot, Laura Schoppe, Rewati Tappu, Jan Haas, Ulrich Laufs, Diana Martins Bordalo, Susanne Gaul, Marion Müller, Hugo A. Katus, Benjamin Meder |
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| Rok vydání: | 2020 |
| Předmět: |
Cardiomyopathy
Dilated Cancer Research Proline TNNT2 TPM1 macromolecular substances Tropomyosin Biochemistry 03 medical and health sciences Splicing factor Exon 0302 clinical medicine Glutamates Troponin T Genetics Humans Connectin RNA Messenger Molecular Biology 030304 developmental biology Heart Failure 0303 health sciences biology Lysine Alternative splicing Troponin I Intron RNA-Binding Proteins Valine Cell biology Computational Mathematics Cardiovascular and Metabolic Diseases RNA splicing biology.protein Titin RNA Splicing Factors 030217 neurology & neurosurgery |
| Zdroj: | Genomics, proteomicsbioinformatics. 20(1) |
| ISSN: | 2210-3244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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