| The 5' UTR of HIV-1 full-length mRNA and the Tat viral protein modulate the programmed -1 ribosomal frameshift that generates HIV-1 enzymes. | |
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MedLine Citation:
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PMID: 22286970 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Translation of the full-length messenger RNA (mRNA) of the human immunodeficiency virus type 1 (HIV-1) generates the precursor of the viral enzymes via a programmed -1 ribosomal frameshift. Here, using dual-luciferase reporters, we investigated whether the highly structured 5' untranslated region (UTR) of this mRNA, which interferes with translation initiation, can modulate HIV-1 frameshift efficiency. We showed that, when the 5' UTR of HIV-1 mRNA occupies the 5' end of the reporter mRNA, HIV-1 frameshift efficiency is increased about fourfold in Jurkat T-cells, compared with a control dual-luciferase reporter with a short unstructured 5' UTR. This increase was related to an interference with cap-dependent translation initiation by the TAR-Poly(A) region at the 5' end of the messenger. HIV-1 mRNA 5' UTR also contains an internal ribosome entry site (IRES), but we showed that, when the cap-dependent initiation mode is available, the IRES is not used or is weakly used. However, when the ribosomes have to use the IRES to translate the dual-luciferase reporter, the frameshift efficiency is comparable to that of the control dual-luciferase reporter. The decrease in cap-dependent initiation and the accompanying increase in frameshift efficiency caused by the 5' UTR of HIV-1 mRNA is antagonized, in a dose-dependent way, by the Tat viral protein. Tat also stimulates the IRES-dependent initiation and decreases the corresponding frameshift efficiency. A model is presented that accounts for the variations in frameshift efficiency depending on the 5' UTR and the presence of Tat, and it is proposed that a range of frameshift efficiencies is compatible with the virus replication. |
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Authors:
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Johanie Charbonneau; Karine Gendron; Gerardo Ferbeyre; Léa Brakier-Gingras |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-01-27 |
Journal Detail:
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Title: RNA (New York, N.Y.) Volume: 18 ISSN: 1469-9001 ISO Abbreviation: RNA Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-16 Completed Date: 2012-04-12 Revised Date: 2013-04-15 |
Medline Journal Info:
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Nlm Unique ID: 9509184 Medline TA: RNA Country: United States |
Other Details:
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Languages: eng Pagination: 519-29 Citation Subset: IM |
Affiliation:
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Département de biochimie, Université de Montréal, Montréal, Québec H3T1J4, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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5' Untranslated Regions
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genetics* Frameshifting, Ribosomal / genetics* Gene Expression Regulation, Viral Gene Order Gene Products, tat / metabolism* Genes, Reporter Genetic Vectors HEK293 Cells HIV-1 / enzymology, genetics*, metabolism Humans Jurkat Cells RNA, Messenger / chemistry* RNA, Viral / chemistry* |
| Grant Support | |
ID/Acronym/Agency:
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HOP-86864//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/5' Untranslated Regions; 0/Gene Products, tat; 0/RNA, Messenger; 0/RNA, Viral |
| Comments/Corrections | |
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