Abstract
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.
Highlights
Cells mount several defenses against viral infection
The RNA interference (RNAi) machinery processes structured double-stranded RNA (dsRNA) hairpins into microRNAs, another class of small RNAs that modulate gene expression [6]. miRNAs are derived from transcription of large highly structured precursors of ϳ70 nucleotides encoded by cellular genes
The exact details of how loss of TAR RNA-binding protein (TRBP) leads to suppression of RNAi remain incompletely understood and somewhat contested [13, 14]; consistent with TRBP’s the currently inferred physiological role of TRBP in the defense against foreign nucleic acids of the cell, this protein was first cloned and identified by us based on its avid binding to a small HIV-1 hairpin RNA, TAR [15]
Summary
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 281, NO. 38, pp. 27674 –27678, September 22, 2006 Printed in the U.S.A. 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. Relevant to the mechanism of RNAi, long double-stranded RNA (dsRNA) originating from viruses are first recognized inside cells by an RNase III enzyme, Dicer, which cleaves the RNA into smaller 21- to 23-nucleotide duplexes, commonly termed small interfering RNAs (siRNA). For this activity, Dicer is assisted by a protein-protein complex formed with a cellular RNA-binding protein called TAR RNA-binding protein (TRBP) [3, 4]. TRBP from Dicer-RISC and reduce RNA silencing in human cells
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