A role for RNA helicase A in post-transcriptional regulation of HIV type 1

Retroviruses must bypass the tight coupling of splicing and nuclear export of mRNA in their replication cycle because unspliced genomic RNA and incomp letely spliced mRNA must be exported to the cytoplasm for packaging or tran slation. This process is mediated by a cis-acting constitutive transport el ement (CTE) for simple retroviruses and by the trans-acting viral protein R ev in concert with its response element (RRE) for complex retroviruses (e.g ., HIV), Recently, we identified RNA helicase A (RHA) as a potential cellul ar cofactor for CTE. Here, we report that RHA also plays a role in Rev/RRE- mediated gene expression and HIV replication. RHA binds weakly to HIV-1 RRE independently of Rev. Overexpression of RHA, but not of an RHA mutant lack ing helicase activity, increased both ReV/RRE- and CTE-dependent gene expre ssion and the levels of unspliced HIV mRNA, Microinjection of antibodies to RHA into nuclei dramatically inhibited both CTE and Rev-dependent gene exp ression in human cells. Exogenous RHA cDNA, but not the mutant RHA, rescued this inhibition. We propose that RHA is required to release both CTE- and RRE-containing mRNA from spliceosomes before completion of splicing, thus f reeing them for nuclear export.