GSBS Student Publications

Title

A protein sensor for siRNA asymmetry

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology

Date

11-20-2004

Document Type

Article

Medical Subject Headings

Animals; 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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

To 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.

Rights and Permissions

Citation: Science. 2004 Nov 19;306(5700):1377-80. Link to article on publisher's site

DOI of Published Version

10.1126/science.1102755

Related Resources

Link to Article in PubMed

Journal Title

Science (New York, N.Y.)

PubMed ID

15550672