Biomedical research institute
     
    You are here: Home / Institute / Seminars and clubs / Exploring the mechanistic strategies of silencing machineries to execute the post-transcriptional repression of messenger RNAs

    Exploring the mechanistic strategies of silencing machineries to execute the post-transcriptional repression of messenger RNAs

    •  

    Seminar Institut Cochin

    Thursday 4 June 2020 - 12:00 - Room conference Rosalind Franklin, 2nd floor

     


    Clément Chapat

    UMR7654 CNRS, Laboratoire de Biochimie (BIOC) de
    l'Ecole Polytechnique, Palaiseau

     

     invited by Isabelle Dusanter

    Institut Cochin, 22 rue Méchain, 75014 Paris

     

    Abstract

    Post-transcriptional silencing mechanisms modulate global and transcript-specific mRNA stability and translation, contributing to the rapid and flexible control of gene expression. mRNA silencing relies on a variety of non-coding RNAs, such as microRNAs, RNA-binding proteins and mRNA modifications. All these features are enriched in the 3’-untranslated region (3’UTR) of mRNAs which acts as a regulatory platform to recruit silencing machineries. Through proteomic-based screening for protein interactions in human cells, we recently observed that 3′UTR-driven factors nucleate a large interaction network containing distinct activities such as cap-binding, translation repression, mRNA deadenylation, decapping and degradation. Notably, we identified the cap-binding eIF4E-Homologous Protein 4EHP as an integral component of post-transcriptional silencing mechanisms through competing with the translation initiation factor eIF4E for binding to the mRNA 5´cap. We described a mechanism wherein 4EHP and its interacting partners engender a closed loop mRNA conformation that blocks translational initiation of microRNA targets. Beyond microRNA action, novel comprehensive interactomes of key 3’UTR-driven factors will be presented to illustrate how these networks of silencing factors can be shaped. Overall, these interactomes shed light on how 3'UTRs instigate common mechanistic strategies to dictate the fate of mRNAs, providing the groundwork for understanding the complex spatial relationships connecting a variety of post-transcriptional regulatory pathways.

     

     

    Message for people not personnal to the Cochin Institute who wish to come to listen to Clément Chapat:
    thank you to send your name, surname and professionnal address by mail to