A role of RNA helicase A in cis-acting transactivation response element-mediated transcriptional regulation of human immunodeficiency virus type 1

RNA helicase A (RHA) has two double-stranded (ds) RNA-binding domains (dsRB D1 and dsRBD2). These domains are conserved with the cis-acting transactiva tion response element (TAR)-binding protein (TRBP) and dsRNA-activated prot ein kinase (PKR). TRBP and PKR are involved in the regulation of HIV-1 gene expression through their binding to TAR RNA. This study shows that RHA als o plays an important role in TAR-mediated HIV-1 gene expression. Wild-type RHA preferably bound to TAR RNA in vitro and in vivo. Overexpression of wil d type RHA strongly enhanced viral mRNA synthesis and virion production as well as HIV-1 long terminal repeat-directed reporter (luciferase) gene expr ession. Substitution of lysine for glutamate at residue 236 in dsRBD2 (RHA( K236E)) reduced its affinity for TAR RNA and impaired HIV-1 transcriptional activity. These results indicate that TAR RNA is a preferred target of RHA dsRBDs and that RHA enhances HIV-1 transcription in vivo in part through t he TAR-binding of RHA.