Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila
- Authors
- Lim, Do Hwan; Kim, Jung; Kim, Sanguk; Carthew, Richard W.; Lee, Young Sik
- Issue Date
- 4-7월-2008
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- RNA interference; siRNA; Drosophila; mutation; dicer-2; R2D2
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.371, no.3, pp.525 - 530
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 371
- Number
- 3
- Start Page
- 525
- End Page
- 530
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/123034
- DOI
- 10.1016/j.bbrc.2008.04.118
- ISSN
- 0006-291X
- 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
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