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Structural domains within the HIV ‐1 mRNA and the ribosomal protein S25 influence cap‐independent translation initiation
Author(s) -
Carvajal Felipe,
Vallejos Maricarmen,
Walters Beth,
Contreras Nataly,
Hertz Marla I.,
Olivares Eduardo,
Cáceres Carlos J.,
Pino Karla,
Letelier Alejandro,
Thompson Sunnie R.,
LópezLastra Marcelo
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13756
Subject(s) - internal ribosome entry site , eukaryotic small ribosomal subunit , translation (biology) , eukaryotic ribosome , initiation factor , eukaryotic translation , ribosome , eukaryotic initiation factor , biology , ribosomal rna , microbiology and biotechnology , protein biosynthesis , ribosomal protein , messenger rna , rna , computational biology , genetics , gene
The 5′ leader of the HIV ‐1 genomic RNA is a multifunctional region that folds into secondary/tertiary structures that regulate multiple processes during viral replication including translation initiation. In this work, we examine the internal ribosome entry site ( IRES ) located in the 5′ leader that drives translation initiation of the viral Gag protein under conditions that hinder cap‐dependent translation initiation. We show that activity of the HIV ‐1 IRES relies on ribosomal protein S25 (eS25). Additionally, a mechanistic and mutational analysis revealed that the HIV ‐1 IRES is modular in nature and that once the 40S ribosomal subunit is recruited to the IRES , translation initiates without the need of ribosome scanning. These findings elucidate a mechanism of initiation by the HIV ‐1 IRES whereby a number of highly structured sites present within the HIV ‐1 5′ leader leads to the recruitment of the 40S subunit directly at the site of initiation of protein synthesis.