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.