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UMass Chan Affiliations
Department of Medicine, Division of Endocrinology and MetabolismDepartment of Biochemistry and Molecular Pharmacology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2003-10-22Keywords
Adenosine Diphosphate; Adenosine Triphosphate; Animals; Base Pair Mismatch; Base Pairing; Base Sequence; Drosophila melanogaster; Hydrogen Bonding; Kinetics; MicroRNAs; Models, Biological; Phosphorylation; RNA Helicases; *RNA Interference; RNA, Antisense; RNA, Double-Stranded; RNA, Messenger; RNA, Small Interfering; RNA, Untranslated; RNA-Induced Silencing Complex; Superoxide DismutaseLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5' ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.Source
Cell. 2003 Oct 17;115(2):199-208.
DOI
10.1016/S0092-8674(03)00759-1Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32517PubMed ID
14567917Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/S0092-8674(03)00759-1