Prevention of dsRNA-induced interferon signaling by AGO1x is linked to breast cancer cell proliferation.
Fiche publication
Date publication
août 2020
Journal
The EMBO journal
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PFEFFER Sébastien
Tous les auteurs :
Ghosh S, Guimaraes JC, Lanzafame M, Schmidt A, Syed AP, Dimitriades B, Börsch A, Ghosh S, Mittal N, Montavon T, Correia AL, Danner J, Meister G, Terracciano LM, Pfeffer S, Piscuoglio S, Zavolan M
Lien Pubmed
Résumé
Translational readthrough, i.e., elongation of polypeptide chains beyond the stop codon, was initially reported for viral RNA, but later found also on eukaryotic transcripts, resulting in proteome diversification and protein-level modulation. Here, we report that AGO1x, an evolutionarily conserved translational readthrough isoform of Argonaute 1, is generated in highly proliferative breast cancer cells, where it curbs accumulation of double-stranded RNAs (dsRNAs) and consequent induction of interferon responses and apoptosis. In contrast to other mammalian Argonaute protein family members with primarily cytoplasmic functions, AGO1x exhibits nuclear localization in the vicinity of nucleoli. We identify AGO1x interaction with the polyribonucleotide nucleotidyltransferase 1 (PNPT1) and show that the depletion of this protein further augments dsRNA accumulation. Our study thus uncovers a novel function of an Argonaute protein in buffering the endogenous dsRNA-induced interferon responses, different than the canonical function of AGO proteins in the miRNA effector pathway. As AGO1x expression is tightly linked to breast cancer cell proliferation, our study thus suggests a new direction for limiting tumor growth.
Mots clés
Argonaute 1, breast cancer, endogenous dsRNA, interferon response, translation readthrough
Référence
EMBO J.. 2020 Aug 19;:e103922