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Poster De Conférence Année : 2022

Selenoprotein mRNAs, eIF3 and hypermethylated caps

Résumé

In eukaryotes, translation initiation requires multiple complexes of eukaryotic initiation factors (eIFs) to assemble elongation-competent ribosomes to the mRNA. Such complexes trigger mRNA attachment to the small 40S ribosomal subunit, mRNA scanning, and start codon selection, as well as ribosome assembly. Alternative translation initiation mechanisms that do not rely on the eIF4E/m7G interaction have been discovered for the translation of specific mRNAs. We have revealed the existence of such a mechanism in the case of selenoprotein mRNAs. Selenoprotein play an essential role in the antioxidant protection and maintenance of the redox potential of the cells. The synthesis of selenoproteins requires the cotranslational recoding of an in-frame UGASec codon. Interactions between the Selenocysteine Insertion Sequence (SECIS) and the SECIS binding protein 2 (SBP2) in the 3' untranslated region (3'UTR) of selenoprotein mRNAs enable the recruitment of the selenocysteine insertion machinery. Several selenoprotein mRNAs undergo unusual cap hypermethylation (to generate m32,2,7G caps) and are not recognized by the translation initiation factor 4E (eIF4E), but nonetheless translated (Wurth et al., 2014). The presence of this particular cap suggests the existence of an atypical translation initiation mechanism for these mRNAs. Cap-dependent mechanisms, involving the eIF3 translation initiation factor as a substitute of eIF4E for the cap recognition has been found (Lee et al., 2015). The human eukaryotic translation initiation factor 3 (eIF3), composed of 13 subunits (a-m), can selectively recruit several cellular mRNAs and plays roles in specialized translation initiation. Here, we analysed the ability of eIF3 to interact with selenoprotein mRNAs. By combining ribonucleoprotein immunoprecipitation (RNP IP) in vivo and in vitro with cross-linking experiments we found interactions between eIF3 and a subgroup of selenoprotein mRNAs. We showed that eIF3 appears to preferentially interact with the group of hypermethylated capped selenoprotein mRNAs rather than m7G- capped mRNAs. We identified direct contacts between GPx1 mRNA and eIF3 c, d, e subunits and showed the existence of common interaction patterns for all hypermethylated capped selenoprotein mRNAs (Hayek et al., in press). Differential interactions of eIF3 with selenoprotein mRNAs can trigger specific translation pathways independent of eIF4E. eIF3 could represent a new player in the translation regulation of selenoprotein expression.
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Dates et versions

hal-03800008 , version 1 (06-10-2022)

Identifiants

  • HAL Id : hal-03800008 , version 1

Citer

Hassan Hayek, Béatrice Chane-Woon-Ming, Laure Schaeffer, Franck Martin, Gilbert Eriani, et al.. Selenoprotein mRNAs, eIF3 and hypermethylated caps. 12th SifrARN, Bordeaux, Oct 2022, Bordeaux, France. ⟨hal-03800008⟩

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