Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties
Department of Biochemistry and Molecular Pharmacology
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
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.
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Citation: Cell. 2012 Nov 21;151(5):1055-67. doi: 10.1016/j.cell.2012.10.036. Link to article on publisher's site
Wee, LiangMeng; Flores-Jasso, Carlos Fabian; Salomon, William E.; and Zamore, Phillip D., "Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties" (2012). Biochemistry and Molecular Pharmacology Publications and Presentations. Paper 160.