HIV-1 tar RNA subverts RNA interferencein transfected cells through sequestration of tar RNA binding protein, TRBP

doi:10.1074/jbc.C600072200

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Papers In Press, published online ahead of print August 3, 2006
J. Biol. Chem, 10.1074/jbc.C600072200
Submitted on March 22, 2006
Accepted on August 3, 2006

HIV-1 tar RNA subverts RNA interferencein transfected cells through sequestration of tar RNA binding protein, TRBP

Yamina Bennasser, Man Lung Yeung, and Kuan-Teh Jeang

National Institute of Allergy & Infectious Diseases, Bethesda, MD 20892-0460

Corresponding Author: kj7e{at}nih.gov

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 cell’s RNA interference (RNAi) apparatus. Human TRBP was originally characterized and cloned fifteen 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.

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