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. 2019 Feb 1;218:31-37.
doi: 10.1016/j.lfs.2018.12.008. Epub 2018 Dec 5.

MiR-219 Represses Expression of dFMR1 in Drosophila Melanogaster

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MiR-219 Represses Expression of dFMR1 in Drosophila Melanogaster

Chao Wang et al. Life Sci. .

Abstract

Aims: Fragile X mental retardation protein (FMRP) plays a vital role in mRNA trafficking and translation inhibition to regulate the synthesis of local proteins in neuronal axons and dendritic terminals. However, there are no reports on microRNA (miRNA)-mediated regulation of FMRP levels in Drosophila. Here, we aimed to identify miRNAs regulating FMRP levels in Drosophila.

Main methods: Using online software, we predicted and selected 11 miRNAs potentially acting on the Drosophila fragile X mental retardation 1 (dFMR1) transcript. These candidates were screened for modulation of dFMR1 transcript levels at the cellular level using a dual luciferase reporter system. In addition, we constructed a transgenic Drosophila model overexpressing miR-219 in the nervous system and quantified dFMRP by western blotting. The neuromuscular junction phenotype in the model was studied by immunofluorescence staining.

Key findings: Among the 11 miRNAs screened, miR-219 and miR-960 reduced luciferase gene activity by binding to the 3'-UTR of the dFMR1 transcript. Mutation of the miR-219 or miR-960 binding sites on the transcript resulted in complete or partial elimination of the miRNA-induced repression. Western blots revealed that dFMRP expression was decreased in the miR-219 overexpression model (Elav>miR-219). Drosophila larvae overexpressing miR-219 showed morphological abnormalities at the neuromuscular junction (increased synaptic boutons and synaptic branches). This finding is consistent with some phenotypes observed in dfmr1 mutants.

Significance: Our results suggest that miR-219 regulates dFMR1 expression in Drosophila and is involved in fragile X syndrome pathogenesis. Collectively, these findings expand the current understanding of miRNA-mediated regulation of target molecule-related functions.

Keywords: Drosophila; NMJ; Screening; dFMR1; miR-219.

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