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.

Institut Gustave Roussy Université Paris Sud UMR 1015 Villejuif France

Université de Brest Inserm EFS UMR 1078 GGB F 29200 Brest France

Université Paris 7 Inserm UMR 1162 Paris France

Université Paris 7 Inserm UMR 1162 Paris France ICCVS University of Gdańsk Science ul Wita Stwosza 63 80 308 Gdańsk Poland

Université Paris 7 Inserm UMR 1162 Paris France ICCVS University of Gdańsk Science ul Wita Stwosza 63 80 308 Gdańsk Poland Department of Medical Biosciences Umeå University Umeå Sweden RECAMO Masaryk Memorial Cancer Institute Zluty kopec 7 656 53 Brno Czech Republic

Université Paris 7 IUH Inserm UMR S 1131 Paris France

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