Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2023

Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress

Jérémy Sandoz
  • Function : Author
Max Cigrang
Amélie Zachayus
  • Function : Author
Philippe Catez
  • Function : Author
Lise-Marie Donnio
  • Function : Author
Clèmence Elly
  • Function : Author
Jadwiga Nieminuszczy
Pietro Berico
Cathy Braun
  • Function : Author
Sergey Alekseev
  • Function : Author
Jean-Marc Egly
  • Function : Author
Wojciech Niedzwiedz
Giuseppina Giglia-Mari
Emmanuel Compe

Abstract

Abstract 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.

Dates and versions

hal-03991051 , version 1 (15-02-2023)

Identifiers

Cite

Jérémy Sandoz, Max Cigrang, Amélie Zachayus, Philippe Catez, Lise-Marie Donnio, et al.. Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress. Nature Communications, 2023, 14 (1), pp.341. ⟨10.1038/s41467-023-35922-5⟩. ⟨hal-03991051⟩
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