A conserved motif in human BTG1 and BTG2 proteins mediates interaction with the poly(A) binding protein PABPC1 to stimulate mRNA deadenylation.
Fiche publication
Date publication
juin 2021
Journal
RNA biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SERAPHIN Bertrand
Tous les auteurs :
Amine H, Ripin N, Sharma S, Stoecklin G, Allain FH, Séraphin B, Mauxion F
Lien Pubmed
Résumé
Antiproliferative BTG/Tob proteins interact directly with the CAF1 deadenylase subunit of the CCR4-NOT complex. This binding requires the presence of two conserved motifs, boxA and boxB, characteristic of the BTG/Tob APRO domain. Consistently, these proteins were shown to stimulate mRNA deadenylation and decay in several instances. Two members of the family, BTG1 and BTG2, were reported further to associate with the protein arginine methyltransferase PRMT1 through a motif, boxC, conserved only in this subset of proteins. We recently demonstrated that BTG1 and BTG2 also contact the first RRM domain of the cytoplasmic poly(A) binding protein PABPC1. To decipher the mode of interaction of BTG1 and BTG2 with partners, we performed nuclear magnetic resonance experiments as well as mutational and biochemical analyses. Our data demonstrate that, in the context of an APRO domain, the boxC motif is necessary and sufficient to allow interaction with PABPC1 but, unexpectedly, that it is not required for BTG2 association with PRMT1. We show further that the presence of a boxC motif in an APRO domain endows it with the ability to stimulate deadenylation and . Overall, our results identify the molecular interface allowing BTG1 and BTG2 to activate deadenylation, a process recently shown to be necessary for maintaining T-cell quiescence.
Mots clés
CCR4-NOT complex, RNA decay, antiproliferative activity, apro domain, cancer, deadenylase, poly(A) binding protein PABPC, poly(A) tail, protein arginine methylase PRMT1, regulation of gene expression
Référence
RNA Biol. 2021 Jun 1;:1-16