Role of RNA helicases in HIV-1 replication

Jeang, Kuan-Teh; Yedavalli, Venkat

For HIV-1, two recent studies provide clues that RNA helicases may also serve co-factor function for transcription from the viral long terminal repeat (LTR). Fujii et al. (39) observed that RHA conserves in its N-terminus two double-stranded RNA-binding (dsRBD) domains characterized previously for the TAR RNA-binding protein, TRBP (40, 41) . These investigators found in both reporter and virus replication assays that RHA activated, in a TAR RNA-binding dependant manner, HIV-1 LTR-directed transcription (39 roles in transcription or indirectly influence the milieu of polymerase II initiation/elongation at the LTR. Downstream from transcription, the fate of HIV-1 encoded RNA is regulated at the step of export of unspliced/partially spliced moieties from the nucleus into the cytoplasm. Unspliced and partially spliced viral RNAs code for genomic RNAs that are packaged into progeny virions and structural proteins. Hence, the egress of these RNAs from the nucleus into the cytoplasm is critical to the life cycle of the virus. Exit of HIV RNAs from the nucleus is a significant issue because unspliced/partially spliced cellular mRNAs are routinely retained in and not permitted export from the nucleus (43) (44) (45) (46) . A large body of work has suggested an elegant solution to this conundrum. Thus, it was established that the HIV-1 encoded Rev protein binds a highly secondary structured element (Rev responsive element; RRE) present in all unspliced and partially spliced HIV transcripts (47) (48) (49) (50) (51) (52) (53) (54) (55) (56) (57) ; and this binding specifically distinguishes, for purposes of nuclear export, viral transcripts from cellular RNAs.