Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila
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SCOPUS
- Title
- Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila
- Authors
- Lim, DH; Kim, J; Kim, S; Carthew, RW; Lee, YS
- Date Issued
- 2008-07-04
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Abstract
- The Drosophila RNase III enzyme Dicer-2 processes double-stranded RNA (dsRNA) precursors into small interfering RNAs (siRNAs). It also interacts with the siRNA product and R2D2 protein to facilitate the assembly of an RNA-induced silencing complex (RISC) that mediates RNA interference. Here, we characterized six independent missense mutations in the dicer-2 gene. Four mutations (P8S, L188F, R269W, and P365L) in the DExH helicase domain reduced dsRNA processing activity. Two mutations were located within an RNase III domain. P1496L caused a loss of dsRNA processing activity comparable to a null dicer-2 mutation. A1453T strongly reduced both dsRNA processing and RISC activity, and decreased the levels of Dicer-2 and R2D2 proteins, suggesting that this mutation destabilizes Dicer-2. We also found that the carboxyl-terminal region of R2D2 is essential for Dicer-2 binding. These results provide further insight into the structure-function relationship of Dicer, which plays a critical role in the siRNA pathway. (C) 2008 Elsevier Inc. All rights reserved
- Keywords
- RNA interference; siRNA; Drosophila; mutation; dicer-2; R2D2; DOUBLE-STRANDED-RNA; INTERFERENCE; COMPLEXES; MECHANISM; CLEAVAGE; R2D2
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/22735
- DOI
- 10.1016/j.bbrc.2008.04.118
- ISSN
- 0006-291X
- Article Type
- Article
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 371, no. 3, page. 525 - 530, 2008-07-04
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