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

Cardiomyopathy, Dilated / genetics Connectin / genetics Glutamates Heart Failure / genetics Humans Lysine Proline RNA Splicing Factors RNA, Messenger / metabolism RNA-Binding Proteins / genetics Tropomyosin / metabolism Troponin I / metabolism Troponin T / metabolism Valine

Dilated cardiomyopathy KHDRBS3 SLM2 Splicing Titin

Journal

Genomics, proteomics & bioinformatics

ISSN: 2210-3244

Titre abrégé: Genomics Proteomics Bioinformatics

Pays: China

ID NLM: 101197608

Informations de publication

Date de publication:
02 2022

Historique:

received: 09 12 2020

accepted: 01 02 2021

pubmed: 18 7 2021

medline: 28 9 2022

entrez: 17 7 2021

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.gpb.2021.01.006 PMID: 34273561 PMC: PMC9510876

pubmed: 34273561

pii: S1672-0229(21)00146-7

doi: 10.1016/j.gpb.2021.01.006

pmc: PMC9510876

pii:

doi:

Substances chimiques

Connectin 0

Glutamates 0

KHDRBS3 protein, human 0

RNA Splicing Factors 0

RNA, Messenger 0

RNA-Binding Proteins 0

Tropomyosin 0

Troponin I 0

Troponin T 0

Proline 9DLQ4CIU6V

Valine HG18B9YRS7

Lysine K3Z4F929H6

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

129-146

Informations de copyright

Références

Nat Genet. 2006 Apr;38(4):411-3

pubmed: 16501576

J Neurosci. 2012 Apr 11;32(15):5024-38

pubmed: 22496549

Circulation. 1996 Mar 1;93(5):841-2

pubmed: 8598070

Science. 2012 Dec 21;338(6114):1593-9

pubmed: 23258891

Elife. 2016 Dec 13;5:

pubmed: 27960072

Hum Genet. 2017 Sep;136(9):1043-1057

pubmed: 28391524

Dev Cell. 2009 Apr;16(4):528-38

pubmed: 19386262

J Leukoc Biol. 2001 Jul;70(1):113-20

pubmed: 11435493

Cell Rep. 2016 Dec 20;17(12):3269-3280

pubmed: 28009295

J Cardiovasc Transl Res. 2013 Dec;6(6):945-55

pubmed: 23775418

J Struct Biol. 2002 Jan-Feb;137(1-2):194-205

pubmed: 12064946

Hum Mutat. 2016 Mar;37(3):269-79

pubmed: 26666891

PLoS One. 2018 Jun 11;13(6):e0198492

pubmed: 29889873

Nat Commun. 2016 Jan 13;7:10355

pubmed: 26758068

Biochem J. 2009 Jan 1;417(1):15-27

pubmed: 19061484

PLoS One. 2012;7(8):e42697

pubmed: 22876330

EMBO J. 2004 Feb 25;23(4):885-96

pubmed: 14963485

Genomics Proteomics Bioinformatics. 2016 Aug;14(4):200-6

pubmed: 27475404

Annu Rev Neurosci. 2013 Jul 8;36:243-70

pubmed: 23701460

Nat Commun. 2012;3:1121

pubmed: 23047679

Nat Rev Genet. 2014 Dec;15(12):829-45

pubmed: 25365966

Circulation. 2018 Sep 25;138(13):1330-1342

pubmed: 29650543

Nature. 2017 Oct 11;550(7675):204-213

pubmed: 29022597

Cell. 2005 Jan 14;120(1):59-72

pubmed: 15652482

Nature. 2015 Jun 25;522(7557):444-449

pubmed: 26083752

Nature. 2010 Jan 21;463(7279):364-8

pubmed: 20010808

Cell Rep. 2015 Mar 10;10(9):1521-1533

pubmed: 25753418

Nucleic Acids Res. 2017 Apr 20;45(7):4120-4130

pubmed: 27994030

PLoS Genet. 2013 Apr;9(4):e1003474

pubmed: 23637638

Nucleic Acids Res. 2018 Jun 1;46(10):5227-5238

pubmed: 29518215

Dev Cell. 2014 Oct 13;31(1):87-99

pubmed: 25313962

Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7):

pubmed: 21441581

Genes Dev. 2010 Nov 1;24(21):2343-64

pubmed: 21041405

Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3276-81

pubmed: 21300889

Genome Res. 2020 Feb;30(2):214-226

pubmed: 31992613

Genomics Proteomics Bioinformatics. 2016 Aug;14(4):179-80

pubmed: 27071812

J Am Coll Cardiol. 2017 Aug 22;70(8):975-991

pubmed: 28818208

Circulation. 2017 Oct 17;136(16):1528-1544

pubmed: 28838933

J Clin Invest. 2016 Jan;126(1):195-206

pubmed: 26619120

Arterioscler Thromb Vasc Biol. 2016 Jul;36(7):1425-33

pubmed: 27199445

Biochim Biophys Acta Mol Basis Dis. 2017 Aug;1863(8):2056-2063

pubmed: 27825848

Curr Protoc Hum Genet. 2015 Oct 06;87:11.16.1-11.16.14

pubmed: 26439713

Curr Pharm Des. 2016;22(31):4744-4751

pubmed: 27396593

J Clin Invest. 2001 Jul;108(2):169-73

pubmed: 11457867

J Cell Sci. 2015 Aug 15;128(16):3030-40

pubmed: 26116573

Int J Cardiol. 2017 Dec 15;249:282-286

pubmed: 28916354

Adv Exp Med Biol. 2007;623:123-47

pubmed: 18380344

Nat Med. 2012 May;18(5):766-73

pubmed: 22466703

Genes Dev. 2010 Jun 1;24(11):1073-4

pubmed: 20516191

Cell Rep. 2014 Mar 27;6(6):1139-1152

pubmed: 24613350

Cardiovasc Res. 2012 Jun 1;94(3):418-27

pubmed: 22345307

Eur Heart J. 2017 Dec 07;38(46):3449-3460

pubmed: 29029073

Indian J Hum Genet. 2010 May;16(2):67-71

pubmed: 21031054