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4 - MicroRNAs in limb development
- from I - Discovery of microRNAs in various organisms
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- By Danielle M. Maatouk, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Jason R. Rock, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Brian D. Harfe, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
- Edited by Krishnarao Appasani
- Foreword by Sidney Altman, Victor R. Ambros
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- Book:
- MicroRNAs
- Published online:
- 22 August 2009
- Print publication:
- 20 December 2007, pp 58-69
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- Chapter
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Summary
Introduction
The vertebrate limb is a highly organized structure that must be patterned along three axes during development: anteroposterior, dorsoventral, and proximodistal (Tickle, 2003). For decades, the limb has served as a choice model system for developmental biologists because of the ease with which it can be manipulated and an organism's ability to survive with abnormal or absent limbs. Despite years of intense investigation, many of the molecules responsible for limb pattern formation are still not known.
Recently, a class of non-coding RNAs, the microRNAs (miRNAs), have been implicated in limb development. These molecules are ~22 nt in their mature form and can bind to mRNAs, leading to their degradation or inhibition of protein production (McManus and Sharp, 2002). The first miRNA to be discovered, lin-4, was identified in a forward genetic screen aimed at identifying developmental timing defects in C. elegans (Lee et al., 1993). Nearly a decade after the discovery of lin-4 in nematodes, a second miRNA, let-7, was identified in organisms ranging from C. elegans to humans (Pasquinelli et al., 2000; Reinhart et al., 2000). In the years since, at least 326 miRNAs have been validated in humans and 249 in mouse (Griffiths-Jones, 2004). Only a few of these miRNAs have known functions (reviewed in Harfe (2005)). Our lab is interested in the role miRNAs play in patterning the vertebrate limb.
MicroRNA processing
Mature miRNAs are produced through two cleavage events by members of the RNaseIII family of nucleases (Bernstein et al., 2001; Hutvagner et al., 2001; Ketting et al., 2001; Lee et al. 2003).