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

Genomics, Proteomics & Bioinformatics 2022年第1期20卷 129-146页

作者： Jes-Niels Boeckel Maximilian Mobius-Winkler Marion Muller 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-Bomeke Benjamin Meder Department of Cardiology Angiology and PneumologyUniversity Hospital HeidelbergD-69120 HeidelbergGermany Klinik und Poliklinik fur Kardiologie Universitatskrankenhaus LeipzigD-04103 LeipzigGermany German Center for Cardiovascular Research(DZHK) Partner site HeidelbergD-69120 HeidelbergGermany Clinic for General and Interventional Cardiology/Angiology Herz-und Diabeteszentrum NRWRuhr-Universitat BochumD-32545 Bad OeynhausenGermany Department of Cardiology and Pneumology University HospitalGeorg-August University GoettingenD-37075 GoettingenGermany German Center for Cardiovascular Research(DZHK) Partner site GoettingenD-37075 GoettingenGermany Berlin Institute for Medical Systems Biology Max Delbruck Center for Molecular Medicine in the Helmholtz AssociationD-10115 BerlinGermany Institute of Biology Humboldt Universitat zu BerlinD-10099 BerlinGermany Neuromuscular and Cardiovascular Cell Biology Max Delbruck Center for Molecular Medicine in the Helmholtz AssociationD-13092 BerlinGermany German Center for Cardiovascular Research(DZHK) Partner site BerlinD-10117 BerlinGermany Stanford Genome Technology Center Department of GeneticsStanford Medical SchoolPalo AltoCA 94304USA

Alternative mRNA splicing is a fundamental process to increase the versatility of the *** humans,cardiac mRNA splicing is involved in the pathophysiology of heart *** in the splicing factor RNA binding motif protein 20(RBM20) cause severe forms of *** 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) *** the human heart,SLM2 binds to important transcripts of sarcomere constituents,such as those encoding myosin light chain2(MYL2),troponin 13(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 *** 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.

关键词： Splicing Titin Dilated cardiomyopathy KHDRBS3 SLM2

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