Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 01 2023
20 01 2023
Historique:
received:
20
06
2022
accepted:
06
01
2023
entrez:
20
1
2023
pubmed:
21
1
2023
medline:
25
1
2023
Statut:
epublish
Résumé
The transcriptional response to genotoxic stress involves gene expression arrest, followed by recovery of mRNA synthesis (RRS) after DNA repair. We find that the lack of the EXD2 nuclease impairs RRS and decreases cell survival after UV irradiation, without affecting DNA repair. Overexpression of wild-type, but not nuclease-dead EXD2, restores RRS and cell survival. We observe that UV irradiation triggers the relocation of EXD2 from mitochondria to the nucleus. There, EXD2 is recruited to chromatin where it transiently interacts with RNA Polymerase II (RNAPII) to promote the degradation of nascent mRNAs synthesized at the time of genotoxic attack. Reconstitution of the EXD2-RNAPII partnership on a transcribed DNA template in vitro shows that EXD2 primarily interacts with an elongation-blocked RNAPII and efficiently digests mRNA. Overall, our data highlight a crucial step in the transcriptional response to genotoxic attack in which EXD2 interacts with elongation-stalled RNAPII on chromatin to potentially degrade the associated nascent mRNA, allowing transcription restart after DNA repair.
Identifiants
pubmed: 36670096
doi: 10.1038/s41467-023-35922-5
pii: 10.1038/s41467-023-35922-5
pmc: PMC9859823
doi:
Substances chimiques
Chromatin
0
RNA Polymerase II
EC 2.7.7.-
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
341Subventions
Organisme : Cancer Research UK
ID : A24881
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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