CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex.
Amino Acid Sequence
/ genetics
Cell Nucleus
/ genetics
Exons
/ genetics
Gene Knockout Techniques
Humans
Neoplasm Proteins
/ genetics
Nonsense Mediated mRNA Decay
/ genetics
RNA Splicing
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Ribonucleoproteins
/ genetics
Transcriptome
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
accepted:
01
07
2020
revised:
20
05
2020
received:
10
01
2020
pubmed:
6
7
2020
medline:
21
10
2020
entrez:
5
7
2020
Statut:
ppublish
Résumé
The exon junction complex (EJC) is an essential constituent and regulator of spliced messenger ribonucleoprotein particles (mRNPs) in metazoans. As a core component of the EJC, CASC3 was described to be pivotal for EJC-dependent nuclear and cytoplasmic processes. However, recent evidence suggests that CASC3 functions differently from other EJC core proteins. Here, we have established human CASC3 knockout cell lines to elucidate the cellular role of CASC3. In the knockout cells, overall EJC composition and EJC-dependent splicing are unchanged. A transcriptome-wide analysis reveals that hundreds of mRNA isoforms targeted by nonsense-mediated decay (NMD) are upregulated. Mechanistically, recruiting CASC3 to reporter mRNAs by direct tethering or via binding to the EJC stimulates mRNA decay and endonucleolytic cleavage at the termination codon. Building on existing EJC-NMD models, we propose that CASC3 equips the EJC with the persisting ability to communicate with the NMD machinery in the cytoplasm. Collectively, our results characterize CASC3 as a peripheral EJC protein that tailors the transcriptome by promoting the degradation of EJC-dependent NMD substrates.
Identifiants
pubmed: 32621609
pii: 5867419
doi: 10.1093/nar/gkaa564
pmc: PMC7470949
doi:
Substances chimiques
CASC3 protein, human
0
Neoplasm Proteins
0
RNA, Messenger
0
RNA-Binding Proteins
0
Ribonucleoproteins
0
messenger ribonucleoprotein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8626-8644Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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