Journal
VIROLOGY
Volume 392, Issue 2, Pages 178-185Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.06.050
Keywords
HuR; ITAF; IRES; HIV-1; HCV; Translation initiation
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Funding
- FONDECYT [1060655, 1090318]
- FONDAP [13980001, PFB12/2007]
- NCIC (National Cancer Institute of Canada) [018125]
- VRAID Pontificia Universidad Catolica de Chile
- MECESUP-Universidad Andres Bello
- MIFAB Institute
- CONICYT
- Terry Fox Foundation
- National Cancer Institute of Canada
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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]RES activity and acts as an activator of the HCV]RES. 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. (C) 2009 Elsevier Inc. All rights reserved.
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