Article

Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA.

Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.
Journal of Biological Chemistry (impact factor: 4.77). 07/2007; 282(24):17649-57. DOI:10.1074/jbc.M611768200 pp.17649-57
Source: PubMed

ABSTRACT 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.

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Keywords

current model
 
Dicer
 
Dicer-containing complex
 
double-stranded RNA-binding protein TRBP
 
generates siRNA
 
human TRBP
 
mammalian cells
 
Mammalian Dicer interacts
 
micro-RNA processing
 
PACT form
 
PACT function
 
PKR
 
regulatory activities
 
RNA interference
 
short hairpin RNA
 
significant inhibition
 
siRNA
 
siRNA production
 
TRBP
 
triple complex