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

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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.

Malbert-Colas, Laurence (författare)
Lista, Maria Jose (författare)
Daskalogianni, Chrysoula (författare)
Apcher, Sebastien (författare)
Pla, Marika (författare)
Findakly, Sarah (författare)
Blondel, Marc (författare)
Fåhraeus, RobinUmeå universitet,Patologi,Universite Paris 7, Paris, France; ICCVS, University of Gdansk, Science, Gdansk, Poland; RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic(Swepub:umu)rofa0013 (författare)
Umeå universitetPatologi (creator_code:org_t)

Ingår i:Nucleic Acids Research: Oxford University Press47:6, s. 3086-31000305-10481362-4962

Av författaren/redakt...: Martins, Rodrigo ...; Malbert-Colas, L ...; Lista, Maria Jos ...; Daskalogianni, C ...; Apcher, Sebastie ...; Pla, Marika; visa fler...; Findakly, Sarah; Blondel, Marc; Fåhraeus, Robin; visa färre...

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