The steady-state level of the nervous-system-specific microRNA-124a is regulated by dFMR1 in Drosophila.
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.
Xu
Xia-Lian
XL
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California 94158, USA.
Li
Yan
Y
Wang
Fay
F
Gao
Fen-Biao
FB
D000818:Animals; D060565:Argonaute Proteins; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009420:Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology
D060565:Argonaute Proteins; D029721:Drosophila Proteins; D039642:Eukaryotic Initiation Factors; D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs; D020365:RNA Helicases; D043244:Ribonuclease III; C489654:AGO1 protein, Drosophila; C467328:FMR1 protein, Drosophila; C509207:MIRN124 microRNA, human; C515033:Dcr-1 protein, Drosophila