Substrate Selectivity of Exportin 5 and Dicer in the Biogenesis of MicroRNAs
Open Access
- 1 January 2006
- journal article
- review article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Symposia on Quantitative Biology
- Vol. 71, 59-66
- https://doi.org/10.1101/sqb.2006.71.050
Abstract
Each step in the biogenesis of microRNAs (miRNAs) depends on recognition of a correct substrate and efficient transport orprocessing of that RNA. Exportin5 (Exp5) and Dicer are proteins that mediate two key steps in this cascade, the nuclear exportand cytoplasmic processing of microRNA precursor (pre-miRNAs). Xenopus laevis oocytes, eggs, and embryos constituteconvenient experimental systems in which to study the substrate specificity of these proteins because specific RNAs or proteinscan be injected directly into different subcellular compartments. We have used the Xenopus system and in vitro processingto define and compare the specificities of Exp5 and Dicer. Although both proteins act on many of the same substrates, weshow that they recognize different structure elements of these RNAs. Our studies also revealed several unexpected activities.For example, Exp5 can mediate export of unspliced pre-mRNAs and excised lariat introns if these RNAs contain an aptamersequence that itself is an Exp5 export substrate. Finally, we demonstrate that maturation of Xenopus oocytes into eggs leadsto a large increase in Dicer activity, suggesting that miRNA biogenesis is subject to developmental control.Keywords
This publication has 39 references indexed in Scilit:
- Lessons from Nature: microRNA-based shRNA librariesNature Methods, 2006
- Suppression of RNA Interference by Adenovirus Virus-Associated RNAJournal of Virology, 2005
- MicroRNAs: Genomics, Biogenesis, Mechanism, and FunctionCell, 2004
- Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAsRNA, 2004
- Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNAThe EMBO Journal, 2002
- Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasmThe EMBO Journal, 2002
- A System for Stable Expression of Short Interfering RNAs in Mammalian CellsScience, 2002
- Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell linesProceedings of the National Academy of Sciences of the United States of America, 2001
- Role for a bidentate ribonuclease in the initiation step of RNA interferenceNature, 2001
- Two helices plus a linker: a small model substrate for eukaryotic RNase P.Proceedings of the National Academy of Sciences of the United States of America, 1995