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Mol Cell. 2010 Jun 25;38(6):900-7. doi: 10.1016/j.molcel.2010.06.014.

MicroRNA biogenesis via splicing and exosome-mediated trimming in Drosophila.

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  • 1Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA.

Abstract

microRNAs (miRNAs) are approximately 22 nucleotide regulatory RNAs derived from hairpins generated either by Drosha cleavage (canonical substrates) or by splicing and debranching of short introns (mirtrons). The 5' end of the highly conserved Drosophila mirtron-like locus mir-1017 is coincident with the splice donor, but a substantial "tail" separates its hairpin from the 3'splice acceptor. Genetic and biochemical studies define a biogenesis pathway involving splicing, lariat debranching, and RNA exosome-mediated "trimming," followed by conventional dicing and loading into AGO1 to yield a miRNA that can repress seed-matched targets. Analysis of cloned small RNAs yielded six additional candidate 3' tailed mirtrons in D. melanogaster. Altogether, these data reveal an unexpected role for the exosome in the biogenesis of miRNAs from hybrid mirtron substrates.

Copyright (c) 2010 Elsevier Inc. All rights reserved.

PMID:
20620959
[PubMed - indexed for MEDLINE]
PMCID:
PMC2904328
Free PMC Article

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