Transcriptome alterations in myotonic dystrophy skeletal muscle and heart.
Adult
Alternative Splicing
/ genetics
Base Sequence
Female
Gene Expression Profiling
/ methods
Heart
/ physiology
Humans
Male
Microsatellite Repeats
/ genetics
Muscle, Skeletal
/ metabolism
Myocardium
/ metabolism
Myotonic Dystrophy
/ genetics
Principal Component Analysis
RNA
/ genetics
RNA Splicing
/ genetics
RNA-Binding Proteins
/ metabolism
Transcriptome
/ genetics
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
30
07
2018
revised:
30
11
2018
accepted:
10
12
2018
pubmed:
19
12
2018
medline:
2
7
2019
entrez:
19
12
2018
Statut:
ppublish
Résumé
Myotonic dystrophy (dystrophia myotonica, DM) is a multi-systemic disease caused by expanded CTG or CCTG microsatellite repeats. Characterized by symptoms in muscle, heart and central nervous system, among others, it is one of the most variable diseases known. A major pathogenic event in DM is the sequestration of muscleblind-like proteins by CUG or CCUG repeat-containing RNAs transcribed from expanded repeats, and differences in the extent of MBNL sequestration dependent on repeat length and expression level may account for some portion of the variability. However, many other cellular pathways are reported to be perturbed in DM, and the severity of specific disease symptoms varies among individuals. To help understand this variability and facilitate research into DM, we generated 120 RNASeq transcriptomes from skeletal and heart muscle derived from healthy and DM1 biopsies and autopsies. A limited number of DM2 and Duchenne muscular dystrophy samples were also sequenced. We analyzed splicing and gene expression, identified tissue-specific changes in RNA processing and uncovered transcriptome changes strongly correlating with muscle strength. We created a web resource at http://DMseq.org that hosts raw and processed transcriptome data and provides a lightweight, responsive interface that enables browsing of processed data across the genome.
Identifiants
pubmed: 30561649
pii: 5250729
doi: 10.1093/hmg/ddy432
pmc: PMC6452195
doi:
Substances chimiques
RNA-Binding Proteins
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1312-1321Subventions
Organisme : NIH HHS
ID : DP5 OD017865
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007413
Pays : United States
Organisme : Wellcome Trust
ID : 107562/Z/15/Z
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : R01 AR060733
Pays : United States
Organisme : Medical Research Council
ID : G0802629
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL045565
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS048843
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR045653
Pays : United States
Organisme : NHGRI NIH HHS
ID : RC2 HG005624
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS048843
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Références
Nat Commun. 2013;4:2480
pubmed: 24048253
Sci Rep. 2018 Apr 12;8(1):5885
pubmed: 29651162
Cell Rep. 2015 Aug 18;12(7):1159-68
pubmed: 26257173
Mol Cell. 2002 Jul;10(1):35-44
pubmed: 12150905
Ann Neurol. 2010 Mar;67(3):291-300
pubmed: 20373340
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Mol Cell. 2007 Oct 12;28(1):68-78
pubmed: 17936705
J Clin Invest. 2012 Dec;122(12):4461-72
pubmed: 23160194
Ann Neurol. 2013 Dec;74(6):862-72
pubmed: 23929620
Ann Neurol. 2011 Apr;69(4):681-90
pubmed: 21400563
Nat Methods. 2010 Dec;7(12):1009-15
pubmed: 21057496
PLoS Genet. 2016 Sep 28;12(9):e1006316
pubmed: 27681373
Cell. 1992 Feb 21;68(4):799-808
pubmed: 1310900
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):260-5
pubmed: 21173221
Hum Mol Genet. 2018 Aug 15;27(16):2789-2804
pubmed: 29771332
Hum Mol Genet. 2012 Mar 15;21(6):1312-24
pubmed: 22140091
Hum Mol Genet. 2013 Feb 15;22(4):704-16
pubmed: 23139243
Nat Struct Mol Biol. 2011 Jun 19;18(7):840-5
pubmed: 21685920
Cell Rep. 2014 Jan 30;6(2):336-45
pubmed: 24412363
Hum Mol Genet. 2011 Jan 1;20(1):1-15
pubmed: 21044947
Nucleic Acids Res. 2010 Apr;38(7):2467-84
pubmed: 20071745
Nat Commun. 2016 Apr 11;7:11067
pubmed: 27063795
Science. 2001 Aug 3;293(5531):864-7
pubmed: 11486088
PLoS One. 2014 Sep 11;9(9):e107324
pubmed: 25211016
Mol Cell. 2002 Jul;10(1):45-53
pubmed: 12150906
EMBO J. 2004 Aug 4;23(15):3103-12
pubmed: 15257297
J Clin Invest. 2017 Feb 1;127(2):549-563
pubmed: 28067669
Cell. 2012 Aug 17;150(4):710-24
pubmed: 22901804
Mol Cell. 2014 Oct 23;56(2):311-322
pubmed: 25263597
Science. 1998 May 1;280(5364):737-41
pubmed: 9563950
Neuron. 2012 Aug 9;75(3):437-50
pubmed: 22884328
Genome Res. 2015 Jun;25(6):858-71
pubmed: 25883322
Nat Med. 2011 Jun;17(6):720-5
pubmed: 21623381