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 Fahraeus

Abstract

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 froma 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.
Author Rodrigo Prado Martins
Rodrigo Prado Martins,,
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, Laurence Malbert-Colas
Laurence Malbert-Colas,,
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, María José Lista
María José Lista,,
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, Chrysoula Daskalogianni (ICCVS)
Chrysoula Daskalogianni,,
- International Centre for Cancer Vaccine Science
, Sebastien Apcher
Sebastien Apcher,,
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, Marika Pla
Marika Pla,,
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, Sarah Findakly
Sarah Findakly,,
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, Marc Blondel
Marc Blondel,,
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, Robin Fahraeus (ICCVS)
Robin Fahraeus,,
- International Centre for Cancer Vaccine Science
Journal seriesNucleic Acids Research, ISSN 0305-1048, (N/A 200 pkt)
Issue year2019
Vol47
No6
Pages3086-3100
Publication size in sheets0.7
ASJC Classification1311 Genetics
DOIDOI:10.1093/nar/gky1296
URL https://doi.org/10.1093/nar/gky1296
Languageen angielski
LicenseOther; published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)200
ScoreMinisterial score = 200.0, 30-09-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 2.657; WoS Impact Factor: 2017 = 11.561 (2) - 2017=10.235 (5)
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