TY - JOUR
T1 - Nuclear processing of nascent transcripts determines synthesis of full-length proteins and antigenic peptides
AU - Martins, Rodrigo Prado
AU - Malbert-Colas, Laurence
AU - Lista, María José
AU - Daskalogianni, Chrysoula
AU - Apcher, Sebastien
AU - Pla, Marika
AU - Findakly, Sarah
AU - Blondel, Marc
AU - Fåhraeus, Robin
N1 - Publisher Copyright:
© The Author(s) 2019.
PY - 2019/4/8
Y1 - 2019/4/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064483672&partnerID=8YFLogxK
U2 - 10.1093/nar/gky1296
DO - 10.1093/nar/gky1296
M3 - Article
C2 - 30624716
AN - SCOPUS:85064483672
SN - 0305-1048
VL - 47
SP - 3086
EP - 3100
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 6
ER -