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PMID: 20620959 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular cell ·Vol. 38 ·No. 6 ·2010-06-25 ·Pages 900-7

Flynt AS, Greimann JC, Chung WJ, Lima CD, Lai EC

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.

MeSH Terms
Animals Argonaute Proteins Base Sequence Drosophila Proteins/metabolism Drosophila melanogaster/genetics,metabolism Eukaryotic Initiation Factors/metabolism Exosomes/physiology Genome, Insect Introns MicroRNAs/genetics,metabolism Molecular Sequence Data RNA Splicing
Chemicals
AGO1 protein, Drosophila Argonaute Proteins Drosophila Proteins Eukaryotic Initiation Factors MicroRNAs
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Flynt Alex S
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA.
Greimann Jaclyn C
Chung Wei-Jen
Lima Christopher D
Lai Eric C
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2010.06.014
Published
2010-06-25
Pages
900-7
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2904328
Subset
IM
Grants
NIGMS NIH HHS · GM083300 · United States
NIGMS NIH HHS · R01 GM079196-04 · United States
NIGMS NIH HHS · R01 GM079196-03 · United States
NIGMS NIH HHS · GM079196 · United States
NHGRI NIH HHS · HG004261 · United States
NHGRI NIH HHS · U01 HG004261 · United States
NIGMS NIH HHS · R01 GM083300-04 · United States
NIGMS NIH HHS · R01 GM083300 · United States
NIGMS NIH HHS · R01 GM079196-02 · United States
NHGRI NIH HHS · U01 HG004261-04 · United States
NIGMS NIH HHS · R01 GM079196 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2010.06.014 PMC Full Text View journal details
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