Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA
Copyright policy )Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA
Mammalian Dicer interacts with double-stranded RNA-binding protein TRBP or PACT to mediate RNA interference and micro-RNA processing. TRBP and PACT are structurally related but exert opposite regulatory activities on PKR. It is not understood whether TRBP and PACT are simultaneously required for Dicer. Here we show that TRBP directly interacts with PACT in vitro and in mammalian cells. TRBP and PACT form a triple complex with Dicer and facilitate the production of small interfering RNA (siRNA) by Dicer. Knockdown of both TRBP and PACT in cultured cells leads to significant inhibition of gene silencing mediated by short hairpin RNA but not by siRNA, suggesting that TRBP and PACT function primarily at the step of siRNA production. Taken together, these findings indicate that human TRBP and PACT directly interact with each other and associate with Dicer to stimulate the cleavage of double-stranded or short hairpin RNA to siRNA. Our work significantly alters the current model for the assembly and function of the Dicer-containing complex that generates siRNA and micro-RNA in human.
- University of Hong Kong China (People's Republic of)
- University of Hong Kong (香港大學) China (People's Republic of)
Male, Ribonuclease III, 571, Small Interfering - genetics - metabolism, Recombinant Fusion Proteins, Nuclear Receptor Coactivators, Intracellular Signaling Peptides and Proteins, RNA-Binding Proteins, RNA, Small Interfering - genetics - metabolism, Mice, Multiprotein Complexes, Testis, Fluorescence Resonance Energy Transfer, Animals, Humans, Nucleic Acid Conformation, RNA, Gene Silencing, Intracellular Signaling Peptides and Proteins - genetics - metabolism, RNA, Small Interfering, Protein Binding
Male, Ribonuclease III, 571, Small Interfering - genetics - metabolism, Recombinant Fusion Proteins, Nuclear Receptor Coactivators, Intracellular Signaling Peptides and Proteins, RNA-Binding Proteins, RNA, Small Interfering - genetics - metabolism, Mice, Multiprotein Complexes, Testis, Fluorescence Resonance Energy Transfer, Animals, Humans, Nucleic Acid Conformation, RNA, Gene Silencing, Intracellular Signaling Peptides and Proteins - genetics - metabolism, RNA, Small Interfering, Protein Binding
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