Back to Search
Start Over
Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila
- Source :
-
Biochemical & Biophysical Research Communications . Jul2008, Vol. 371 Issue 3, p525-530. 6p. - Publication Year :
- 2008
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *RNA
*RIBOSE
*NUCLEIC acids
*CATALYTIC RNA
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 371
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 32177543
- Full Text :
- https://doi.org/10.1016/j.bbrc.2008.04.118