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PMID: 21482538 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Activity of the human immunodeficiency virus type 1 cell cycle-dependent internal ribosomal entry site is modulated by IRES trans-acting factors.

Nucleic acids research ·Vol. 39 ·No. 14 ·2011-08-00 ·Pages 6186-200

Vallejos M, Deforges J, Plank TD, Letelier A, Ramdohr P, Abraham CG, Valiente-Echeverría F, Kieft JS, Sargueil B, López-Lastra M

Abstract

The 5' leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA harbors an internal ribosome entry site (IRES) that is functional during the G2/M phase of the cell cycle. Here we show that translation initiation mediated by the HIV-1 IRES requires the participation of trans-acting cellular factors other than the canonical translational machinery. We used 'standard' chemical and enzymatic probes and an 'RNA SHAPE' analysis to model the structure of the HIV-1 5' leader and we show, by means of a footprinting assay, that G2/M extracts provide protections to regions previously identified as crucial for HIV-1 IRES activity. We also assessed the impact of mutations on IRES function. Strikingly, mutations did not significantly affect IRES activity suggesting that the requirement for pre-formed stable secondary or tertiary structure within the HIV-1 IRES may not be as strict as has been described for other viral IRESes. Finally, we used a proteomic approach to identify cellular proteins within the G2/M extracts that interact with the HIV-1 5' leader. Together, data show that HIV-1 IRES-mediated translation initiation is modulated by cellular proteins.

MeSH Terms
5' Untranslated Regions Base Sequence Cell Cycle/genetics Cytoplasm/metabolism HIV-1/genetics HeLa Cells Humans Molecular Sequence Data Nucleic Acid Conformation Peptide Chain Initiation, Translational Point Mutation RNA, Viral/chemistry,metabolism RNA-Binding Proteins/metabolism Regulatory Sequences, Ribonucleic Acid
Chemicals
5' Untranslated Regions RNA, Viral RNA-Binding Proteins Regulatory Sequences, Ribonucleic Acid
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Vallejos Maricarmen
Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia, Centro de Investigaciones Médicas, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile.
Deforges Jules
Plank Terra-Dawn M
Letelier Alejandro
Ramdohr Pablo
Abraham Christopher G
Valiente-Echeverría Fernando
Kieft Jeffrey S
Sargueil Bruno
López-Lastra Marcelo
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkr189
Published
2011-08-00
Epub
2011-00-10
Pages
6186-200
Language
English
Region
England
NLM ID
0411011
PMCID
PMC3152342
Subset
IM
Grants
NIGMS NIH HHS · GM-72560 · United States
NIGMS NIH HHS · GM-81346 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1093/nar/gkr189 PMC Full Text View journal details
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