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Han, B.W., Hung, J.H., Weng, Z., Zamore, P.D., Ameres, S.L. (2011). The 3'-to-5' Exoribonuclease Nibbler Shapes the 3' Ends of MicroRNAs Bound to Drosophila Argonaute1.  Curr. Biol. 21(22): 1878--1887.
FlyBase ID
FBrf0216729
Publication Type
Research paper
Abstract

MicroRNAs (miRNAs) are ~22 nucleotide (nt) small RNAs that control development, physiology, and pathology in animals and plants. Production of miRNAs involves the sequential processing of primary hairpin-containing RNA polymerase II transcripts by the RNase III enzymes Drosha in the nucleus and Dicer in the cytoplasm. miRNA duplexes then assemble into Argonaute proteins to form the RNA-induced silencing complex (RISC). In mature RISC, a single-stranded miRNA directs the Argonaute protein to bind partially complementary sequences, typically in the 3' untranslated regions of messenger RNAs, repressing their expression.Here, we show that after loading into Argonaute1 (Ago1), more than a quarter of all Drosophila miRNAs undergo 3' end trimming by the 3'-to-5' exoribonuclease Nibbler (CG9247). Depletion of Nibbler by RNA interference (RNAi) reveals that miRNAs are frequently produced by Dicer-1 as intermediates that are longer than ~22 nt. Trimming of miRNA 3' ends occurs after removal of the miRNA* strand from pre-RISC and may be the final step in RISC assembly, ultimately enhancing target messenger RNA repression. In vivo, depletion of Nibbler by RNAi causes developmental defects.We provide a molecular explanation for the previously reported heterogeneity of miRNA 3' ends and propose a model in which Nibbler converts miRNAs into isoforms that are compatible with the preferred length of Ago1-bound small RNAs.

PubMed ID
PubMed Central ID
PMC3236499 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Curr. Biol.
    Title
    Current Biology
    Publication Year
    1991-
    ISBN/ISSN
    0960-9822
    Data From Reference