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PMID: 17599402 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila.

Cell ·Vol. 130 ·No. 1 ·2007-07-13 ·Pages 89-100

Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC

Abstract

The canonical microRNA (miRNA) pathway converts primary hairpin precursor transcripts into approximately 22 nucleotide regulatory RNAs via consecutive cleavages by two RNase III enzymes, Drosha and Dicer. In this study, we characterize Drosophila small RNAs that derive from short intronic hairpins termed "mirtrons." Their nuclear biogenesis appears to bypass Drosha cleavage, which is essential for miRNA biogenesis. Instead, mirtron hairpins are defined by the action of the splicing machinery and lariat-debranching enzyme, which yield pre-miRNA-like hairpins. The mirtron pathway merges with the canonical miRNA pathway during hairpin export by Exportin-5, and both types of hairpins are subsequently processed by Dicer-1/loqs. This generates small RNAs that can repress perfectly matched and seed-matched targets, and we provide evidence that they function, at least in part, via the RNA-induced silencing complex effector Ago1. These findings reveal that mirtrons are an alternate source of miRNA-type regulatory RNAs.

MeSH Terms
Animals Animals, Genetically Modified Base Sequence Drosophila Proteins/genetics,metabolism Drosophila melanogaster/anatomy & histology,genetics,metabolism Evolution, Molecular Gene Expression Regulation Introns MicroRNAs/genetics,metabolism Models, Genetic Molecular Sequence Data Nucleic Acid Conformation RNA Precursors/chemistry,genetics,metabolism RNA Splicing Recombinant Fusion Proteins/genetics,metabolism Ribonuclease III/genetics,metabolism Signal Transduction/physiology Structure-Activity Relationship
Chemicals
Drosophila Proteins MicroRNAs RNA Precursors Recombinant Fusion Proteins Ribonuclease III drosha protein, Drosophila
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Okamura Katsutomo
Memorial Sloan-Kettering Cancer Center, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10021, USA.
Hagen Joshua W
Duan Hong
Tyler David M
Lai Eric C
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.06.028
Published
2007-07-13
Epub
2007-00-28
Pages
89-100
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2729315
Subset
IM
Grants
NIGMS NIH HHS · R01 GM083300 · United States
NIGMS NIH HHS · R01 GM083300-01 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NIGMS NIH HHS · GM07739 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2007.06.028 PMC Full Text View journal details
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