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

查看全文 作　　者：Jes-Niels [1,2]Boeckel;Maximilian Mobius-[2]Winkler;Marion [1,3,4]Muller;Sabine [5,6]Rebs;Nicole [1]Eger;Laura [1]Schoppe;Rewati [1]Tappu;Karoline [2]E.Kokot;Jasmin [2]M.Kneuer;Susanne [2]Gaul;Diana [1,3]M.Bordalo;Alan [1,3]Lai;Jan [1,3]Haas;Mahsa [7,8]Ghanbari;Philipp Drewe-[7,8]Boss;Martin [9,10]Liss;Hugo [1,3]A.Katus;Uwe [7,8]Ohler;Michael [9,10]Gotthardt;Ulrich [2]Laufs;Katrin Streckfuss-[5,6]Bomeke;Benjamin [1,3,11]Meder

机构地区：[1]Department of Cardiology,Angiology and Pneumology,University Hospital Heidelberg,D-69120 Heidelberg,Germany;[2]Klinik und Poliklinik fur Kardiologie,Universitatskrankenhaus Leipzig,D-04103 Leipzig,Germany;[3]German Center for Cardiovascular Research(DZHK),Partner site Heidelberg,D-69120 Heidelberg,Germany;[4]Clinic for General and Interventional Cardiology/Angiology,Herz-und Diabeteszentrum NRW,Ruhr-Universitat Bochum,D-32545 Bad Oeynhausen,Germany;[5]Department of Cardiology and Pneumology,University Hospital,Georg-August University Goettingen,D-37075 Goettingen,Germany;[6]German Center for Cardiovascular Research(DZHK),Partner site Goettingen,D-37075 Goettingen,Germany;[7]Berlin Institute for Medical Systems Biology,Max Delbruck Center for Molecular Medicine in the Helmholtz Association,D-10115 Berlin,Germany;[8]Institute of Biology,Humboldt Universitat zu Berlin,D-10099 Berlin,Germany;[9]Neuromuscular and Cardiovascular Cell Biology,Max Delbruck Center for Molecular Medicine in the Helmholtz Association,D-13092 Berlin,Germany;[10]German Center for Cardiovascular Research(DZHK),Partner site Berlin,D-10117 Berlin,Germany;[11]Stanford Genome Technology Center,Department of Genetics,Stanford Medical School,Palo Alto,CA 94304,USA

出　　处：《Genomics, Proteomics & Bioinformatics》索引2022年第20卷第1期,共18页

基　　金：supported by grants from the Deutsches Zentrum für Herz-Kreislauf-Forschung(German Center for Cardiovascular Research,DZHK,Germany);the German Ministry of Education and Research(Grant No.FKZ 031L0075B,Ca RNAtion,Germany);the Informatics for Life(Klaus Tschira Foundation,Germany);the Faculty of Medicine of the Leipzig University to MMW;the Dr.Marija Orlovic Stiftung(Grant No.T0395/35973/2020,Germany)to JNB;the European Union(Grant No.FP7 Best Ageing,Europe);supported by an excellence fellowship of the Else Kr?ner Fresenius Foundation(Germany)。 摘　　要：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 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 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. 关键词：SPLICING TITIN Dilated cardiomyopathy KHDRBS3 SLM2

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

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