Structural highlights
Function
[REV_HV1W2] Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm (By similarity).
Publication Abstract from PubMed
The solution structure of a human immunodeficiency virus type-1 (HIV-1) Rev peptide bound to stem-loop IIB of the Rev response element (RRE) RNA was solved by nuclear magnetic resonance spectroscopy. The Rev peptide has an alpha-helical conformation and binds in the major groove of the RNA near a purine-rich internal loop. Several arginine side chains make base-specific contacts, and an asparagine residue contacts a G.A base pair. The phosphate backbone adjacent to a G.G base pair adopts an unusual structure that allows the peptide to access a widened major groove. The structure formed by the two purine-purine base pairs of the RRE creates a distinctive binding pocket that the peptide can use for specific recognition.
Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex.,Battiste JL, Mao H, Rao NS, Tan R, Muhandiram DR, Kay LE, Frankel AD, Williamson JR Science. 1996 Sep 13;273(5281):1547-51. PMID:8703216[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Battiste JL, Mao H, Rao NS, Tan R, Muhandiram DR, Kay LE, Frankel AD, Williamson JR. Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex. Science. 1996 Sep 13;273(5281):1547-51. PMID:8703216
