SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy.

Autor:	Boeckel JN; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; Klinik und Poliklinik für Kardiologie, Universitätskrankenhaus Leipzig, D-04103 Leipzig, Germany., Möbius-Winkler M; Klinik und Poliklinik für Kardiologie, Universitätskrankenhaus Leipzig, D-04103 Leipzig, Germany., Müller M; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner site Heidelberg, D-69120 Heidelberg, Germany; Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, D-32545 Bad Oeynhausen, Germany., Rebs S; Department of Cardiology and Pneumology, University Hospital, Georg-August University Goettingen, D-37075 Goettingen, Germany; German Center for Cardiovascular Research (DZHK), Partner site Goettingen, D-37075 Goettingen, Germany., Eger N; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany., Schoppe L; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany., Tappu R; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany., Kokot KE; Klinik und Poliklinik für Kardiologie, Universitätskrankenhaus Leipzig, D-04103 Leipzig, Germany., Kneuer JM; Klinik und Poliklinik für Kardiologie, Universitätskrankenhaus Leipzig, D-04103 Leipzig, Germany., Gaul S; Klinik und Poliklinik für Kardiologie, Universitätskrankenhaus Leipzig, D-04103 Leipzig, Germany., Bordalo DM; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner site Heidelberg, D-69120 Heidelberg, Germany., Lai A; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner site Heidelberg, D-69120 Heidelberg, Germany., Haas J; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner site Heidelberg, D-69120 Heidelberg, Germany., Ghanbari M; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, D-10115 Berlin, Germany; Institute of Biology, Humboldt Universität zu Berlin, D-10099 Berlin, Germany., Drewe-Boss P; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, D-10115 Berlin, Germany; Institute of Biology, Humboldt Universität zu Berlin, D-10099 Berlin, Germany., Liss M; Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, D-13092 Berlin, Germany; German Center for Cardiovascular Research (DZHK), Partner site Berlin, D-10117 Berlin, Germany., Katus HA; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner site Heidelberg, D-69120 Heidelberg, Germany., Ohler U; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, D-10115 Berlin, Germany; Institute of Biology, Humboldt Universität zu Berlin, D-10099 Berlin, Germany., Gotthardt M; Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, D-13092 Berlin, Germany; German Center for Cardiovascular Research (DZHK), Partner site Berlin, D-10117 Berlin, Germany., Laufs U; Klinik und Poliklinik für Kardiologie, Universitätskrankenhaus Leipzig, D-04103 Leipzig, Germany., Streckfuss-Bömeke K; Department of Cardiology and Pneumology, University Hospital, Georg-August University Goettingen, D-37075 Goettingen, Germany; German Center for Cardiovascular Research (DZHK), Partner site Goettingen, D-37075 Goettingen, Germany., Meder B; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, D-69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner site Heidelberg, D-69120 Heidelberg, Germany; Stanford Genome Technology Center, Department of Genetics, Stanford Medical School, Palo Alto, CA 94304, USA. Electronic address: Benjamin.Meder@med.uni-heidelberg.de.
Jazyk:	angličtina
Zdroj:	Genomics, proteomics & bioinformatics [Genomics Proteomics Bioinformatics] 2022 Feb; Vol. 20 (1), pp. 129-146. Date of Electronic Publication: 2021 Jul 15.
DOI:	10.1016/j.gpb.2021.01.006
Abstrakt:	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. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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