The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites.
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.
Rivas-Aravena
Andrea
A
Instituto Milenio de Inmunología e Inmunoterapia, Jeune Equipe Associée à l'IRD, Centro de Investigaciones Médicas, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Ramdohr
Pablo
P
Vallejos
Maricarmen
M
Valiente-Echeverría
Fernando
F
Dormoy-Raclet
Virginie
V
Rodríguez
Felipe
F
Pino
Karla
K
Holzmann
Cristian
C
Huidobro-Toro
J Pablo
JP
Gallouzi
Imed-Eddine
IE
López-Lastra
Marcelo
M
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D016174:Hepacivirus / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009865:Oocytes; D010442:Peptide Chain Initiation, Translational; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism; D014779:Virus Replication; D014982:Xenopus laevis
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins