Abstract
Background The HIV-1 genomic RNA (gRNA) has several roles in the viral life cycle. In the nucleus, the gRNA is the pre-mRNA that is alternatively and incompletely spliced into mRNAs encoding Tat, Rev, Nef, Vif, Vpr, Vpu and Env. However, approximately 50% of the gRNA remains unspliced and is exported from the nucleus by the viral protein Rev using the CRM1 nuclear export pathway. In the cytoplasm, the gRNA serves as the mRNA for Gag and Gag-Pol and is also packaged into virions. As the gRNA is an unspliced, intron-containing mRNA with a long, highly structured 5’ UTR and rare codon usage in the open reading frames, how it interacts with cellular RNA metabolism and translation machinery to promote abundant Gag expression and infectious virion production remains unclear.
Highlights
The HIV-1 genomic RNA has several roles in the viral life cycle
To identify cellular factors that regulate genomic RNA (gRNA) splicing, abundance and/or translation efficiency, we took advantage of the fact that mouse cells are non-permissive for HIV-1 Gag expression
We screened candidate cDNAs encoding human proteins that interact with the gRNA for their ability to increase Gag expression and virion production in mouse cells
Summary
The HIV-1 genomic RNA (gRNA) has several roles in the viral life cycle. The gRNA is the pre-mRNA that is alternatively and incompletely spliced into mRNAs encoding Tat, Rev, Nef, Vif, Vpr, Vpu and Env. approximately 50% of the gRNA remains unspliced and is exported from the nucleus by the viral protein Rev using the CRM1 nuclear export pathway. The gRNA serves as the mRNA for Gag and Gag-Pol and is packaged into virions. As the gRNA is an unspliced, intron-containing mRNA with a long, highly structured 5’ UTR and rare codon usage in the open reading frames, how it interacts with cellular RNA metabolism and translation machinery to promote abundant Gag expression and infectious virion production remains unclear
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