The 3'-to-5' exoribonuclease Nibbler shapes the 3' ends of microRNAs bound to Drosophila Argonaute1

UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Department of Biochemistry and Molecular Pharmacology



Document Type


Medical Subject Headings

Animals; Argonaute Proteins; Cell Line; Drosophila Proteins; Drosophila melanogaster; Exoribonucleases; MicroRNAs; Polymerase Chain Reaction; RNA Helicases; *RNA Interference; *RNA Processing, Post-Transcriptional; RNA, Messenger; RNA-Induced Silencing Complex; Ribonuclease III


Bioinformatics | Genetics and Genomics | Molecular Biology


BACKGROUND: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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Citation: Curr Biol. 2011 Nov 22;21(22):1878-87. doi: 10.1016/j.cub.2011.09.034. Link to article on publisher's site

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Link to Article in PubMed