Title

Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

11-21-2012

Document Type

Article

Medical Subject Headings

Animals; Argonaute Proteins; Base Sequence; Drosophila Proteins; Drosophila melanogaster; Mice; MicroRNAs; *Models, Biological; *RNA Interference; RNA, Guide; RNA, Small Interfering; RNA-Induced Silencing Complex

Abstract

MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) guide Argonaute proteins to silence mRNA expression. Argonaute binding alters the properties of an RNA guide, creating functional domains. We show that the domains established by Argonaute-the anchor, seed, central, 3' supplementary, and tail regions-have distinct biochemical properties that explain the differences between how animal miRNAs and siRNAs bind their targets. Extensive complementarity between an siRNA and its target slows the rate at which fly Argonaute2 (Ago2) binds to and dissociates from the target. Highlighting its role in antiviral defense, fly Ago2 dissociates so slowly from extensively complementary target RNAs that essentially every fully paired target is cleaved. Conversely, mouse AGO2, which mainly mediates miRNA-directed repression, dissociates rapidly and with similar rates for fully paired and seed-matched targets. Our data narrow the range of biochemically reasonable models for how Argonaute-bound siRNAs and miRNAs find, bind, and regulate their targets.

Rights and Permissions

Citation: Cell. 2012 Nov 21;151(5):1055-67. doi: 10.1016/j.cell.2012.10.036. Link to article on publisher's site

Comments

Co-author LiangMeng Wee is a student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

23178124