Nucleic Acids Research Advance Access published online on April 10, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm153
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HIV controls the selective packaging of genomic, spliced viral and cellular RNAs into virions through different mechanisms
1CPBS, UMI, CNRS, 4 bd Henri IV, CS 69033, 34965 Montpellier, France and Architecture et Réactivité de l’ARN, Université Louis Pasteur, CNRS, IBMC, 15 rue R. Descartes, 67084 Strabourg, France
*To whom correspondence should be addressed. Tel: +33 4 67 60 02 32; Fax: +33 4 67 60 44 20; Email: mmougel{at}univ-montp1.fr
Received January 18, 2007. Revised February 27, 2007. Accepted February 28, 2007.
In addition to genomic RNA, HIV-1 particles package cellular and spliced viral RNAs. In order to determine the encapsidation mechanisms of these RNAs, we determined the packaging efficiencies and specificities of genomic RNA, singly and fully spliced HIV mRNAs and different host RNAs species: 7SL RNA, U6 snRNA and GAPDH mRNA using RT-QPCR. Except GAPDH mRNA, all RNAs are selectively encapsidated. Singly spliced RNAs, harboring the Rev-responsible element, and fully spliced viral RNAs, which do not contain this motif, are enriched in virions to similar levels, even though they are exported from the nucleus by different routes. Deletions of key motifs (SL1 and/or SL3) of the packaging signal of genomic RNA indicate that HIV and host RNAs are encapsidated through independent mechanisms, while genomic and spliced viral RNA compete for the same trans-acting factor due to the presence of the 5' common exon containing the TAR, poly(A) and U5-PBS hairpins. Surprisingly, the RNA dimerization initiation site (DIS/SL1) appears to be the main packaging determinant of genomic RNA, but is not involved in packaging of spliced viral RNAs, suggesting a functional interaction with intronic sequences. Active and selective packaging of host and spliced viral RNAs provide new potential functions to these RNAs in the early stages of the virus life cycle.
The authors wish it to be known that, in their opinion, the second and third authors should be regarded as joint second Authors.
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