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Title: The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites

Abstract

The human embryonic-lethal abnormal vision (ELAV)-like protein, HuR, has been recently found to be involved in the regulation of protein synthesis. In this study we show that HuR participates in the translational control of the HIV-1 and HCV IRES elements. HuR functions as a repressor of HIV-1 IRES activity and acts as an activator of the HCV IRES. The effect of HuR was evaluated in three independent experimental systems, rabbit reticulocyte lysate, HeLa cells, and Xenopus laevis oocytes, using both overexpression and knockdown approaches. Furthermore, results suggest that HuR mediated regulation of HIV-1 and HCV IRESes does not require direct binding of the protein to the RNA nor does it need the nuclear translocation of the IRES-containing RNAs. Finally, we show that HuR has a negative impact on post-integration steps of the HIV-1 replication cycle. Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression.

Authors:
; ; ;  [1];  [2];  [3]; ;  [1];  [3];  [2];  [1]
  1. Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e Inmunoterapia, Jeune Equipe Associee a l'IRD, Centro de Investigaciones Medicas, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, Santiago (Chile)
  2. Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Quebec (Canada)
  3. Centro de Regulacion Celular y Patologia, J. V. Luco e Instituto Milenio de Biologia Fundamental y Aplicada, MIFAB, Departamento de Fisiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)
Publication Date:
OSTI Identifier:
21357542
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 392; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2009.06.050; PII: S0042-6822(09)00412-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; CONTROL; HELA CELLS; OOCYTES; PROTEINS; RABBITS; REGULATIONS; SYNTHESIS; ANIMAL CELLS; ANIMALS; GERM CELLS; LAWS; MAMMALS; MICROORGANISMS; ORGANIC COMPOUNDS; PARASITES; TUMOR CELLS; VERTEBRATES; VIRUSES

Citation Formats

Rivas-Aravena, Andrea, Ramdohr, Pablo, Vallejos, Maricarmen, Valiente-Echeverria, Fernando, Dormoy-Raclet, Virginie, Rodriguez, Felipe, Pino, Karla, Holzmann, Cristian, Huidobro-Toro, J. Pablo, Gallouzi, Imed-Eddine, and Lopez-Lastra, Marcelo, E-mail: malopez@med.puc.c. The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites. United States: N. p., 2009. Web. doi:10.1016/j.virol.2009.06.050.
Rivas-Aravena, Andrea, Ramdohr, Pablo, Vallejos, Maricarmen, Valiente-Echeverria, Fernando, Dormoy-Raclet, Virginie, Rodriguez, Felipe, Pino, Karla, Holzmann, Cristian, Huidobro-Toro, J. Pablo, Gallouzi, Imed-Eddine, & Lopez-Lastra, Marcelo, E-mail: malopez@med.puc.c. The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites. United States. doi:10.1016/j.virol.2009.06.050.
Rivas-Aravena, Andrea, Ramdohr, Pablo, Vallejos, Maricarmen, Valiente-Echeverria, Fernando, Dormoy-Raclet, Virginie, Rodriguez, Felipe, Pino, Karla, Holzmann, Cristian, Huidobro-Toro, J. Pablo, Gallouzi, Imed-Eddine, and Lopez-Lastra, Marcelo, E-mail: malopez@med.puc.c. Wed . "The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites". United States. doi:10.1016/j.virol.2009.06.050.
@article{osti_21357542,
title = {The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites},
author = {Rivas-Aravena, Andrea and Ramdohr, Pablo and Vallejos, Maricarmen and Valiente-Echeverria, Fernando and Dormoy-Raclet, Virginie and Rodriguez, Felipe and Pino, Karla and Holzmann, Cristian and Huidobro-Toro, J. Pablo and Gallouzi, Imed-Eddine and Lopez-Lastra, Marcelo, E-mail: malopez@med.puc.c},
abstractNote = {The human embryonic-lethal abnormal vision (ELAV)-like protein, HuR, has been recently found to be involved in the regulation of protein synthesis. In this study we show that HuR participates in the translational control of the HIV-1 and HCV IRES elements. HuR functions as a repressor of HIV-1 IRES activity and acts as an activator of the HCV IRES. The effect of HuR was evaluated in three independent experimental systems, rabbit reticulocyte lysate, HeLa cells, and Xenopus laevis oocytes, using both overexpression and knockdown approaches. Furthermore, results suggest that HuR mediated regulation of HIV-1 and HCV IRESes does not require direct binding of the protein to the RNA nor does it need the nuclear translocation of the IRES-containing RNAs. Finally, we show that HuR has a negative impact on post-integration steps of the HIV-1 replication cycle. Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression.},
doi = {10.1016/j.virol.2009.06.050},
journal = {Virology},
issn = {0042-6822},
number = 2,
volume = 392,
place = {United States},
year = {2009},
month = {9}
}