The Journal of Neuroscience, November 12, 2008, 28(46):11883-11889; doi:10.1523/JNEUROSCI.4114-08.2008
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Neurobiology of Disease
The Steady-State Level of the Nervous-System-Specific MicroRNA-124a Is Regulated by dFMR1 in Drosophila
Xia-Lian Xu, *
Yan Li, *
Fay Wang, and
Fen-Biao Gao
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California 94158
Correspondence should be addressed to Fen-Biao Gao, Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158. Email: fgao{at}gladstone.ucsf.edu
Fragile X syndrome is the most common form of inherited mental retardation caused by loss of the fragile X mental retardation protein 1 (FMRP). The detailed molecular pathways underlying the pathogenesis of this disorder remain incompletely understood. Here, we show that miR-124a, a nervous-system-specific miRNA, is associated with the Drosophila homolog of FMRP (dFMR1) in vivo. Ectopic expression of wild-type but not mutant miR-124a precursors decreased dendritic branching of dendritic arborization sensory neurons, which was partially rescued by the loss of dFMR1 activity, suggesting that the biogenesis and/or function of miR-124a are partially dependent on dFMR1. Indeed, in contrast with the complete loss of mature miR-124a in Dicer-1 mutants, steady-state levels of endogenous or ectopically expressed mature miR-124a were partially reduced in dfmr1 mutants, whereas the level of pre-miR-124a increased. This effect could be explained in part by the reduced abundance of the Dicer-1-Ago1 complex in the absence of dFMR1. These findings suggest a modulatory role for dFMR1 to maintain proper levels of miRNAs during neuronal development.
Key words: miR-124a; processing; Drosophila; fragile X syndrome; dendrites; RNA
Received Aug. 28, 2008;
revised Sept. 24, 2008;
accepted Sept. 26, 2008.
Correspondence should be addressed to Fen-Biao Gao, Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158. Email: fgao{at}gladstone.ucsf.edu
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S. Chang, S. Wen, D. Chen, and P. Jin
Small regulatory RNAs in neurodevelopmental disorders
Hum. Mol. Genet.,
April 15, 2009;
18(R1):
R18 - R26.
[Abstract]
[Full Text]
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