Nuclear processing of nascent transcripts determines synthesis of full-length proteins and antigenic peptides

Rodrigo Prado Martins, Laurence Malbert-Colas, María José Lista, Chrysoula Daskalogianni, Sebastien Apcher, Marika Pla, Sarah Findakly, Marc Blondel, Robin Fåhraeus

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    24 Citations (Scopus)

    Résumé

    Peptides presented on major histocompatibility (MHC) class I molecules form an essential part of the immune system’s capacity to detect virus-infected or transformed cells. Earlier works have shown that pioneer translation peptides (PTPs) for the MHC class I pathway are as efficiently produced from introns as from exons, or from mRNAs targeted for the nonsense-mediated decay pathway. The production of PTPs is a target for viral immune evasion but the underlying molecular mechanisms that govern this non-canonical translation are unknown. Here, we have used different approaches to show how events taking place on the nascent transcript control the synthesis of PTPs and full-length proteins. By controlling the subcellular interaction between the G-quadruplex structure (G4) of a gly-ala encoding mRNA and nucleolin (NCL) and by interfering with mRNA maturation using multiple approaches, we demonstrate that antigenic peptides derive from a nuclear non-canonical translation event that is independently regulated from the synthesis of full-length proteins. Moreover, we show that G4 are exploited to control mRNA localization and translation by distinguishable mechanisms that are targets for viral immune evasion.

    langue originaleAnglais
    Pages (de - à)3086-3100
    Nombre de pages15
    journalNucleic Acids Research
    Volume47
    Numéro de publication6
    Les DOIs
    étatPublié - 8 avr. 2019

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