Rev-mediated nuclear export of HIV-1 RNA Authored: Matthews, L, Rice, AP, 2005-07-27 00:00:00 Edited: Matthews, L, 2006-06-07 20:09:58 Pubmed12932730 Pubmed14701878 Pubmed15749819 Pubmed2406030 Pubmed2784194 Pubmed7512159 Pubmed8076606 Pubmed8805303 Pubmed9791012 Reactome Database ID Release 43165054 Reactome, http://www.reactome.org ReactomeREACT_6190 Reviewed: Kumar, A, 2007-01-31 22:47:49 The HIV-1 genome contains 9 genes encoded by a single transcript. In order for the virus to replicate, unspliced, singly-spliced and fully spliced viral mRNA must be exported from the nucleus. The HIV-1 mRNA splice sites are inefficient resulting it the accumulation of a pool of incompletely spliced RNAs (Staffa and Cochrane, 1994). In the early stages of the viral life cycle, or in the absence of the viral Rev protein, completely spliced viral mRNA which encode the regulatory proteins Tat, Nef and Rev are exported from the nucleus while the incompletely spliced structural protein encoding transcripts are held within the nucleus by cellular proteins that normally function in preventing the nuclear export of cellular pre-mRNA. Export of both unspliced and partially spliced mRNA is mediated by the viral protein Rev which is recruited, along with cellular cofactors, to the Rev Response Element (RRE) within the HIV-1 mRNA sequence (Malim et al., 1990; Fischer et al., 1994). The cellular hRIP protein is essential for correct Rev-mediated export of viral RNAs to the cytoplasm (Sanchez-Velar et al., 2004; Yu et al., 2005). PathwayStep3600 PathwayStep3601 PathwayStep3602 PathwayStep3603 PathwayStep3604 PathwayStep3605 PathwayStep3596 PathwayStep3597 PathwayStep3599 PathwayStep3598 Rev molecules assemble onto the RRE RNA sequence through their ARM sequence Rev multimer-bound HIV-1 mRNA:Crm1:Ran:GTP complex associates with the NPC Rev multimer-bound HIV-1 mRNA:CRM1 complex associates with Ran:GTP Association of RanBP1 with Ran-GTP:CRM1:Rev:mRNA complex Translocation of nuclear RNA transport complex to cytoplasm Multimerization of Rev Conversion of Ran-GDP to Ran-GTP Rev multimer-bound HIV-1 mRNA associates with Crm1 Hydrolysis of Ran:GTP to Ran:GDP Release of the HIV-1 mRNA and Crm1 from Rev in the cytoplasm