Role of RNA helicases in HIV-1 replication

Jeang, Kuan-Teh; Yedavalli, Venkat

There is another area where a cellular helicase activity and HIV-1 are likely to intersect. An emerging research focus is the role of small interfering RNAs (87) and microRNAs (miRNA) as innate cell defenses against viruses including HIV-1 (87) (88) (89) (90) . In human cells, the precursor for miRNA (pre-miRNA) is processed by DICER (Figure 2A) which is a ribonuclease with a bona fide RNA helicase domain (91, 92) . A surprising recent finding revealed that the human TRBP, which has been shown to be a potent binder of the HIV-1 TAR RNA RNA (40, 41) , is an indispensable dsRNA-binding partner of DICER which allows the latter to associate with pre-miRNA (91, 92) . Without TRBP, DICER's miRNA processing activity is lost. Thus an intriguing scenario can potentially unfold. Accordingly, whereas the ribonuclease-helicase protein DICER requires TRBP to process duplex-structured miRNAs in order that the cell can use such matured miRNAs for antiviral defense, it could be speculated that HIV-1 has evolved to restrict this defense by the ability to transcribe viral TAR RNA to squelch TRBP away from DICER (Y. Bennasser, M. L. Yeung and K. T. Jeang, manuscript submitted) ( Figure 2B ). If this thinking is correct, then HIV-1 has developed mechanisms not only to co-opt the active functions of a virus-propitious cellular helicase (i.e. DDX3) but also to inactivate the role of a second virus-pernicious helicase (i.e. DICER) for purposes of selfish gain.