Atypical translation mechanism of selenoprotein mRNPs
Résumé
Atypical translation mechanism of selenoprotein mRNPs
Gribling-Burrer A.-S.1, Wurth L.2, Leichter M.1, Massenet, S.2, Martin F1., Eriani G.1, Allmang C.1 1University of Strasbourg, CNRS, Architecture and Reactivity of RNA, Strasbourg, France ; 2 Université de Lorraine, CNRS, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA),Vandoeuvre-lès-Nancy, France
1 Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, Strasbourg, France ; 2 Université de Lorraine, CNRS, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA),Vandoeuvre-lès-Nancy, France
Selenoproteins, key players of oxidative stress protection, are synthesized by co-translational recoding mechanisms of in-frame UGA codons. In mammals, this process is governed by the recruitment of dedicated factors to a hairpin structure, called Selenocysteine Insertion Sequences (SECIS), in the 3’UTR of selenoprotein mRNAs. Essential in this process is the SECIS binding protein 2 (SBP2) that binds the SECIS RNA and recruits translation and assembly factors to the mRNP. SBP2 shares a common RNA binding domain with core proteins of small non-coding RNPs and selenoprotein mRNP assembly is similar to that of snRNPs (splicing) or snoRNPs (ribosome biosynthesis). We have demonstrated that selenoprotein mRNAs also undergo 5' cap maturation events. We showed that several selenoprotein mRNAs, unlike most mammalian mRNAs, bear a hypermethylated m32,2,7G cap instead of a classical 7-methylguanosine (m7G) cap and undergo a similar 5’ end maturation pathway than non-coding RNAs (Wurth et al. 2014). This cap modification is ensured by the enzyme Trimethyl-guanosine synthase (Tgs1) and requires the assembly chaperone complex SMN as well as the methylosome. We have deciphered the cap maturation pathway and analyzed its functional impact on selenoprotein mRNA translation. m32,2,7G capped selenoprotein mRNAs are not efficiently recognized by the canonical translation initiation factor eIF4E but are translated in vivo. Furthermore, our results suggest the existence of an atypical mechanism of translation initiation for selenoprotein mRNAs.