Nuclear processing of nascent transcripts determines synthesis of full-length proteins and antigenic peptides.
Nucleic Acids Res
; 47(6): 3086-3100, 2019 04 08.
Article
em En
| MEDLINE
| ID: mdl-30624716
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 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Biossíntese de Proteínas
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Antígenos de Histocompatibilidade Classe I
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Antígenos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article