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

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    Authors
    Wee, LiangMeng
    Flores-Jasso, Carlos Fabian
    Salomon, William E.
    Zamore, Phillip D.
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2012-11-21
    Keywords
    Animals
    Argonaute Proteins
    Base Sequence
    Drosophila Proteins
    Drosophila melanogaster
    Mice
    MicroRNAs
    *Models, Biological
    *RNA Interference
    RNA, Guide
    RNA, Small Interfering
    RNA-Induced Silencing Complex
    Biochemistry, Biophysics, and Structural Biology
    Genetics and Genomics
    Molecular Genetics
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595543
    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.
    Source

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

    DOI
    10.1016/j.cell.2012.10.036
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/26031
    PubMed ID
    23178124
    Notes

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

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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cell.2012.10.036
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