Rapid Depletion of DIS3, EXOSC10, or XRN2 Reveals the Immediate Impact of Exoribonucleolysis on Nuclear RNA Metabolism and Transcriptional Control.
DIS3
EXOSC10/Rrp6
XRN2
degradation
exosome
non-coding RNA
transcription
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 03 2019
05 03 2019
Historique:
received:
01
10
2018
revised:
09
01
2019
accepted:
04
02
2019
entrez:
7
3
2019
pubmed:
7
3
2019
medline:
6
6
2020
Statut:
ppublish
Résumé
Cell-based studies of human ribonucleases traditionally rely on methods that deplete proteins slowly. We engineered cells in which the 3'→5' exoribonucleases of the exosome complex, DIS3 and EXOSC10, can be rapidly eliminated to assess their immediate roles in nuclear RNA biology. The loss of DIS3 has the greatest impact, causing the substantial accumulation of thousands of transcripts within 60 min. These transcripts include enhancer RNAs, promoter upstream transcripts (PROMPTs), and products of premature cleavage and polyadenylation (PCPA). These transcripts are unaffected by the rapid loss of EXOSC10, suggesting that they are rarely targeted to it. More direct detection of EXOSC10-bound transcripts revealed its substrates to prominently include short 3' extended ribosomal and small nucleolar RNAs. Finally, the 5'→3' exoribonuclease, XRN2, has little activity on exosome substrates, but its elimination uncovers different mechanisms for the early termination of transcription from protein-coding gene promoters.
Identifiants
pubmed: 30840897
pii: S2211-1247(19)30174-3
doi: 10.1016/j.celrep.2019.02.012
pmc: PMC6403362
pii:
doi:
Substances chimiques
RNA, Nuclear
0
RNA
63231-63-0
Exoribonucleases
EC 3.1.-
Exosome Multienzyme Ribonuclease Complex
EC 3.1.-
DIS3 protein, human
EC 3.1.13.-
EXOSC10 protein, human
EC 3.1.13.-
XRN2 protein, human
EC 3.1.13.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2779-2791.e5Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/7
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 095518/Z/11/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107791/Z/15/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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