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
AbstractPeptides 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.
|Journal series||Nucleic Acids Research, ISSN 0305-1048, (A 40 pkt)|
|Publication size in sheets||0.7|
|License||Other; published final; ; with publication|
|Score|| = 40.0, 16-07-2019, ArticleFromJournal|
= 40.0, 16-07-2019, ArticleFromJournal
|Publication indicators||: 2016 = 2.657; : 2017 = 11.561 (2) - 2017=10.235 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.