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- Title
The role of PACT in the RNA silencing pathway.
- Authors
Yoontae Lee; Hur, Inha; Seong-Yeon Park; Young-Kook Kim; Suh, Mi Ra; Kim, V. Narry
- Abstract
Small RNA-mediated gene silencing (RNA silencing) has emerged as a major regulatory pathway in eukaryotes. Identification of the key factors involved in this pathway has been a subject of rigorous investigation in recent years. In humans, small RNAs are generated by Dicer and assembled into the effector complex known as RNA-induced silencing complex (RISC) by multiple factors including hAgo2, the mRNA-targeting endonuclease, and TRBP (HIV-1 TAR RNA-binding protein), a dsRNA-binding protein that interacts with both Dicer and hAgo2. Here we describe an additional dsRNA-binding protein known as PACT, which is significant in RNA silencing. PACT is associated with an ∼500 kDa complex that contains Dicer, hAgo2, and TRBP. The interaction with Dicer involves the third dsRNA-binding domain (dsRBD) of PACT and the N-terminal region of Dicer containing the helicase motif. Like TRBP, PACT is not required for the pre-microRNA (miRNA) cleavage reaction step. However, the depletion of PACT strongly affects the accumulation of mature miRNA in vivo and moderately reduces the efficiency of small interfering RNA-induced RNA interference. Our study indicates that, unlike other RNase III type proteins, human Dicer may employ two different dsRBD-containing proteins that facilitate RISC assembly.
- Subjects
GENE silencing; RNA-protein interactions; CARRIER proteins; DNA helicases; MESSENGER RNA; GENETIC regulation; RNA
- Publication
EMBO Journal, 2006, Vol 25, Issue 3, p522
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7600942