Matranga, Christian B.
Martinez, Natalia Julia
Zamore, Phillip D.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Graduate School of Biomedical Sciences
Document TypeJournal Article
KeywordsAnimals; Dimerization; Drosophila; Drosophila Proteins; Light; Luciferases; Nucleic Acid Conformation; RNA Helicases; *RNA Interference; RNA, Double-Stranded; RNA, Small Interfering; RNA-Binding Proteins; RNA-Induced Silencing Complex; Superoxide Dismutase; Thermodynamics; Uracil
Medicine and Health Sciences
MetadataShow full item record
AbstractTo act as guides in the RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) must be unwound into their component strands, then assembled with proteins to form the RNA-induced silencing complex (RISC), which catalyzes target messenger RNA cleavage. Thermodynamic differences in the base-pairing stabilities of the 5' ends of the two approximately 21-nucleotide siRNA strands determine which siRNA strand is assembled into the RISC. We show that in Drosophila, the orientation of the Dicer-2/R2D2 protein heterodimer on the siRNA duplex determines which siRNA strand associates with the core RISC protein Argonaute 2. R2D2 binds the siRNA end with the greatest double-stranded character, thereby orienting the heterodimer on the siRNA duplex. Strong R2D2 binding requires a 5'-phosphate on the siRNA strand that is excluded from the RISC. Thus, R2D2 is both a protein sensor for siRNA thermodynamic asymmetry and a licensing factor for entry of authentic siRNAs into the RNAi pathway.
SourceScience. 2004 Nov 19;306(5700):1377-80. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32699
PubMed ID15550672; 15550672
Related ResourcesLink to Article in PubMed