Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction.
Aging
Animals
Apoptosis
Carrier Proteins
/ genetics
Cell Survival
Coenzyme A-Transferases
/ genetics
Disease Models, Animal
Gene Silencing
Humans
LIM Domain Proteins
/ genetics
Male
Mice
Mice, Inbred C57BL
Myocardial Infarction
/ genetics
Myocytes, Cardiac
/ cytology
NF-E2-Related Factor 2
/ genetics
RNA, Antisense
/ genetics
RNA, Long Noncoding
/ genetics
RNA, Small Interfering
/ genetics
p300-CBP Transcription Factors
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 04 2020
27 04 2020
Historique:
received:
10
08
2018
accepted:
07
04
2020
entrez:
29
4
2020
pubmed:
29
4
2020
medline:
11
8
2020
Statut:
epublish
Résumé
Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.
Identifiants
pubmed: 32341350
doi: 10.1038/s41467-020-15995-2
pii: 10.1038/s41467-020-15995-2
pmc: PMC7184724
doi:
Substances chimiques
Carrier Proteins
0
Crip2 protein, mouse
0
LIM Domain Proteins
0
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
RNA, Antisense
0
RNA, Long Noncoding
0
RNA, Small Interfering
0
p300-CBP Transcription Factors
EC 2.3.1.48
Coenzyme A-Transferases
EC 2.8.3.-
3-ketoacid CoA-transferase
EC 2.8.3.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2039Subventions
Organisme : Medical Research Council
ID : MC_UP_1102/4
Pays : United Kingdom
Organisme : NCRR NIH HHS
ID : S10 RR025677
Pays : United States
Références
Dev Cell. 2013 Jan 28;24(2):206-14
pubmed: 23369715
Basic Res Cardiol. 2012 Nov;107(6):307
pubmed: 23099820
Circ Res. 2014 Apr 25;114(9):1389-97
pubmed: 24602777
Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):137-45
pubmed: 25359860
Cell Rep. 2016 Oct 18;17(4):1193-1205
pubmed: 27760321
J Am Chem Soc. 2013 May 8;135(18):6766-9
pubmed: 23506098
Mol Cells. 2014 May;37(5):406-11
pubmed: 24823359
RNA Biol. 2013 Oct;10(10):1579-85
pubmed: 24036695
Circulation. 1998 Jan 27;97(3):276-81
pubmed: 9462530
Front Physiol. 2018 Dec 14;9:1794
pubmed: 30618806
Genome Biol. 2016 Feb 16;17:28
pubmed: 26883116
Nature. 2014 Oct 2;514(7520):102-106
pubmed: 25119045
Transcription. 2014;5(4):e944014
pubmed: 25483404
BMC Med Imaging. 2010 Jan 11;10:1
pubmed: 20064248
Nat Med. 2016 Oct;22(10):1131-1139
pubmed: 27618650
Nat Biotechnol. 2016 Feb;34(2):184-191
pubmed: 26780180
J Am Coll Cardiol. 2016 Mar 15;67(10):1214-1226
pubmed: 26965544
Nucleic Acids Res. 2015 Jan;43(Database issue):D670-81
pubmed: 25428374
Epigenetics. 2014 Jan;9(1):13-20
pubmed: 24149621
Cell Chem Biol. 2016 Nov 17;23(11):1325-1333
pubmed: 27773629
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Circ Res. 2015 Feb 13;116(4):737-50
pubmed: 25677520
Nat Protoc. 2017 Jun;12(6):1177-1197
pubmed: 28492526
Circ Res. 2012 Apr 13;110(8):1097-108
pubmed: 22499900
Nucleic Acids Res. 2019 Apr 8;47(6):e32
pubmed: 30698727
Front Cell Dev Biol. 2016 Oct 18;4:110
pubmed: 27803896
BMC Cardiovasc Disord. 2017 Oct 24;17(1):272
pubmed: 29065851
J Clin Invest. 2014 Nov;124(11):4899-914
pubmed: 25271623
Gene Expr Patterns. 2011 Oct;11(7):384-94
pubmed: 21601656
Cell Rep. 2018 Aug 14;24(7):1722-1729
pubmed: 30110629
Nucleic Acids Res. 2015 Jan;43(Database issue):D174-80
pubmed: 25378313
Circ Res. 2015 Jul 3;117(2):192-206
pubmed: 26139858
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Annu Rev Biochem. 2012;81:145-66
pubmed: 22663078
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):157-62
pubmed: 17185421
Nat Commun. 2017 Nov 20;8(1):1614
pubmed: 29158499
Nature. 2013 Mar 7;495(7439):107-10
pubmed: 23426265
Circ Heart Fail. 2013 Nov;6(6):1239-49
pubmed: 24014826
Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):186-92
pubmed: 23325475
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761
pubmed: 29155950
Genome Res. 2002 Apr;12(4):656-64
pubmed: 11932250
Biophys J. 2004 Dec;87(6):3954-73
pubmed: 15377537
FASEB J. 2010 May;24(5):1467-78
pubmed: 20019242
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Nat Biotechnol. 1997 Sep;15(9):871-5
pubmed: 9306402
Sci Transl Med. 2016 Feb 17;8(326):326ra22
pubmed: 26888430
Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1339-46
pubmed: 18467642
Science. 2009 Jun 26;324(5935):1710-3
pubmed: 19460962
Genes Dev. 2009 Jul 1;23(13):1494-504
pubmed: 19571179
Mol Cell. 2015 Nov 19;60(4):626-36
pubmed: 26590717
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
J Immunol Methods. 1986 May 1;89(1):123-30
pubmed: 2422282
Nucleic Acids Res. 2013 Apr 1;41(6):e74
pubmed: 23335781
Nucleic Acids Res. 2013 Jan;41(Database issue):D56-63
pubmed: 23193274
Circ Res. 2008 Nov 21;103(11):1232-40
pubmed: 18845810