RNF219 regulates CCR4-NOT function in mRNA translation and deadenylation

Aude Guénolé (1) , Fabien Velilla (1) , Aymeric Chartier (2) , April Rich (3) , Anne-Ruxandra Carvunis (3) , Claude Sardet (4, 5, 6, 7) , Martine Simonelig (2) , Bijan Sobhian (2, 1)

1 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
2 IGH - Institut de génétique humaine
3 PITT - University of Pittsburgh
4 INSERM - Institut National de la Santé et de la Recherche Médicale
5 UM - Université de Montpellier
6 ICM - Institut régional de Cancérologie de Montpellier
7 CNRS - Centre National de la Recherche Scientifique

Abstract Post-transcriptional regulatory mechanisms play a role in many biological contexts through the control of mRNA degradation, translation and localization. Here, we show that the RING finger protein RNF219 co-purifies with the CCR4-NOT complex, the major mRNA deadenylase in eukaryotes, which mediates translational repression in both a deadenylase activity-dependent and -independent manner. Strikingly, RNF219 both inhibits the deadenylase activity of CCR4-NOT and enhances its capacity to repress translation of a target mRNA. We propose that the interaction of RNF219 with the CCR4-NOT complex directs the translational repressive activity of CCR4-NOT to a deadenylation-independent mechanism.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Cancer

Aude Guénolé, Fabien Velilla, Aymeric Chartier, April Rich, Anne-Ruxandra Carvunis, et al.. RNF219 regulates CCR4-NOT function in mRNA translation and deadenylation. Scientific Reports, 2022, 12 (1), pp.9288. ⟨10.1038/s41598-022-13309-8⟩. ⟨hal-04275608⟩