HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein, TRBP.
TAR RNA-binding protein, TRBP, was recently discovered to be an essential partner for Dicer and a crucial component of the RNA-induced silencing complex (RISC), a critical element of the RNA interference (RNAi) of the cell apparatus. Human TRBP was originally characterized and cloned 15 years ago based on its high affinity for binding the HIV-1 encoded leader RNA, TAR. RNAi is used, in part, by cells to defend against infection by viruses. Here, we report that transfected TAR RNA can attenuate the RNAi machinery in human cells. Our data suggest that TAR RNA sequesters TRBP rendering it unavailable for downstream Dicer-RISC complexes. TAR-induced inhibition of Dicer-RISC activity in transfected cells was partially relieved by exogenous expression of TRBP.
Bennasser
Yamina
Y
Molecular Virology Section, Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.
Yeung
Man Lung
ML
Jeang
Kuan-Teh
KT
D016325:HIV Long Terminal Repeat / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000502:physiology; D012367:RNA, Viral / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D043244:Ribonuclease III / Q000037:antagonists & inhibitors; D014162:Transfection; D000099253:Trans-Activation Responsive RNA-Binding Protein
D034741:RNA, Small Interfering; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D000099253:Trans-Activation Responsive RNA-Binding Protein; C104647:PRKRA protein, human