Intronic Determinants Coordinate Charme lncRNA Nuclear Activity through the Interaction with MATR3 and PTBP1.
CRISPR Cas9
alternative splicing
chromatin
epigenetic control
introns
lncRNA
muscle
myogenesis
nuclear aggregates
ribonucleoparticle
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
22 12 2020
22 12 2020
Historique:
received:
24
07
2020
revised:
27
10
2020
accepted:
02
12
2020
entrez:
28
12
2020
pubmed:
29
12
2020
medline:
22
12
2021
Statut:
ppublish
Résumé
Chromatin architect of muscle expression (Charme) is a muscle-restricted long noncoding RNA (lncRNA) that plays an important role in myogenesis. Earlier evidence indicates that the nuclear Charme isoform, named pCharme, acts on the chromatin by assisting the formation of chromatin domains where myogenic transcription occurs. By combining RNA antisense purification (RAP) with mass spectrometry and loss-of-function analyses, we have now identified the proteins that assist these chromatin activities. These proteins-which include a sub-set of splicing regulators, principally PTBP1 and the multifunctional RNA/DNA binding protein MATR3-bind to sequences located within the alternatively spliced intron-1 to form nuclear aggregates. Consistent with the functional importance of pCharme interactome in vivo, a targeted deletion of the intron-1 by a CRISPR-Cas9 approach in mouse causes the release of pCharme from the chromatin and results in cardiac defects similar to what was observed upon knockout of the full-length transcript.
Identifiants
pubmed: 33357424
pii: S2211-1247(20)31537-0
doi: 10.1016/j.celrep.2020.108548
pmc: PMC7773549
pii:
doi:
Substances chimiques
Heterogeneous-Nuclear Ribonucleoproteins
0
MATR3 protein, human
0
Nuclear Matrix-Associated Proteins
0
PTBP1 protein, human
0
RNA, Long Noncoding
0
RNA-Binding Proteins
0
Polypyrimidine Tract-Binding Protein
139076-35-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108548Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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