3lph

Structural highlights

Function

[REV_HV1H3] 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.^{[1] [2] [3]}

References

1. ↑ Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254-7. PMID:2784194 doi:http://dx.doi.org/10.1038/338254a0
2. ↑ Fridell RA, Bogerd HP, Cullen BR. Nuclear export of late HIV-1 mRNAs occurs via a cellular protein export pathway. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4421-4. PMID:8633082
3. ↑ Sanchez-Velar N, Udofia EB, Yu Z, Zapp ML. hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region. Genes Dev. 2004 Jan 1;18(1):23-34. Epub 2003 Dec 30. PMID:14701878 doi:10.1101/gad.1149704
4. ↑ Daugherty MD, Liu B, Frankel AD. Structural basis for cooperative RNA binding and export complex assembly by HIV Rev. Nat Struct Mol Biol. 2010 Nov;17(11):1337-42. Epub 2010 Oct 17. PMID:20953181 doi:10.1038/nsmb.1902