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. 2015 Aug 24;7(8):4826-35.
doi: 10.3390/v7082846.

New Structure Sheds Light on Selective HIV-1 Genomic RNA Packaging

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Free PMC article

New Structure Sheds Light on Selective HIV-1 Genomic RNA Packaging

Erik D Olson et al. Viruses. .
Free PMC article

Abstract

Two copies of unspliced human immunodeficiency virus (HIV)-1 genomic RNA (gRNA) are preferentially selected for packaging by the group-specific antigen (Gag) polyprotein into progeny virions as a dimer during the late stages of the viral lifecycle. Elucidating the RNA features responsible for selective recognition of the full-length gRNA in the presence of an abundance of other cellular RNAs and spliced viral RNAs remains an area of intense research. The recent nuclear magnetic resonance (NMR) structure by Keane et al. [1] expands upon previous efforts to determine the conformation of the HIV-1 RNA packaging signal. The data support a secondary structure wherein sequences that constitute the major splice donor site are sequestered through base pairing, and a tertiary structure that adopts a tandem 3-way junction motif that exposes the dimerization initiation site and unpaired guanosines for specific recognition by Gag. While it remains to be established whether this structure is conserved in the context of larger RNA constructs or in the dimer, this study serves as the basis for characterizing large RNA structures using novel NMR techniques, and as a major advance toward understanding how the HIV-1 gRNA is selectively packaged.

Keywords: HIV; NMR; RNA structure; psi; retroviral packaging.

Figures

Figure 1
Figure 1
Proposed conformational changes of the HIV-1 5′UTR. (a) In the unspliced monomeric RNA, the dimerization initiation site (DIS) sequence participates in a “fold-back” interaction with the U5, thus exposing the gag start codon (AUG) for translation; (b) The dimerization-competent form of the RNA requires a secondary structure change in which the AUG interacts with the U5 sequence, the major splice donor site/stem-loop 2 (SD/SL2) is sequestered by base pairing with sequences in stem-loop 1 (SL1) and U5, and the DIS is exposed; (c) The exposed DIS in the dimerization-competent conformation is then available to form a “kissing”-loop interaction, resulting in a gRNA homodimer that is eventually stabilized into an extended dimer structure. The sequences in orange, cyan, red, and green represent the primer binding site (PBS), DIS, SD/SL2 and the AUG, respectively.

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