Aberrant RNA methylation triggers recruitment of an alkylation repair complex - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Molecular Cell Année : 2021

Aberrant RNA methylation triggers recruitment of an alkylation repair complex

Chuan He
  • Fonction : Auteur

Résumé

Summary Central to genotoxic responses is their ability to sense highly specific signals to activate the appropriate repair response. We previously reported that the activation of the ASCC-ALKBH3 repair pathway is exquisitely specific to alkylation damage in human cells. Yet the mechanistic basis for the selectivity of this pathway was not immediately obvious. Here, we demonstrate that RNA but not DNA alkylation is the initiating signal for this process. Aberrantly methylated RNA is sufficient to recruit ASCC, while an RNA dealkylase suppresses ASCC recruitment during chemical alkylation. In turn, recruitment of ASCC during alkylation damage, which is mediated by the E3 ubiquitin ligase RNF113A, suppresses transcription and R-loop formation. We further show that alkylated pre-mRNA is sufficient to activate RNF113A E3 ligase in vitro in a manner dependent on its RNA binding Zn-finger domain. Together, our work identifies an unexpected role for RNA damage in eliciting a specific response to genotoxins.
Fichier principal
Vignette du fichier
Tsao et al. RNF113A Mol Cell 2021.pdf (10.64 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03759772 , version 1 (30-08-2022)

Identifiants

Citer

Ning Tsao, Joshua R Brickner, Rebecca Rodell, Adit Ganguly, Matthew Wood, et al.. Aberrant RNA methylation triggers recruitment of an alkylation repair complex. Molecular Cell, 2021, 81 (20), pp.4228-4242.e8. ⟨10.1016/j.molcel.2021.09.024⟩. ⟨hal-03759772⟩
17 Consultations
30 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More