SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy
- Author:
Boeckel JES-NIELS
1
,
2
;
M?bius-Winkler MAXIMILIAN
;
Müller MARION
;
Rebs SABINE
;
Eger NICOLE
;
Schoppe LAURA
;
Tappu REWATI
;
E.Kokot KAROLINE
;
M.Kneuer JASMIN
;
Gaul SUSANNE
;
M.Bordalo DIANA
;
Lai ALAN
;
Haas JAN
;
Ghanbari MAHSA
;
Drewe-Boss PHILIPP
;
Liss MARTIN
;
A.Katus HUGO
;
Ohler UWE
;
Gotthardt MICHAEL
;
Laufs ULRICH
;
Streckfuss-B?meke KATRIN
;
Meder BENJAMIN
Author Information
1. Department of Cardiology,Angiology and Pneumology,University Hospital Heidelberg,D-69120 Heidelberg,Germany
2. Klinik und Poliklinik für Kardiologie,Universit?tskrankenhaus Leipzig,D-04103 Leipzig,Germany
- Keywords:
Splicing;
Titin;
Dilated cardiomyopathy;
KHDRBS3;
SLM2
- From:
Genomics, Proteomics & Bioinformatics
2022;20(1):129-146
- CountryChina
- Language:Chinese
-
Abstract:
Alternative mRNA splicing is a fundamental process to increase the versatility of the gen-ome.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 anal-yses 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 medi-ates 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.
