Drosophila FMRP controls miR-276-mediated regulation of nejire mRNA for space-filling dendrite development

Abstract

MicroRNAs (miRNAs) are enriched in neurons and play important roles in dendritic spine development and synaptic plasticity. miRNA activity is controlled by a wide range of RNA-binding proteins (RBPs). Fragile X mental retardation protein (FMRP), a highly conserved RBP, has been linked to miRNA-mediated gene regulation in axonal development and dendritic spine formation. FMRP also participates in dendritic arbor morphogenesis, but whether and how miRNAs contribute to its function in this process remains to be elucidated. Here, using Drosophila larval sensory neurons, we show that a FMRP-associated miRNA, miR-276, functions in FMRP-mediated space filling dendrite morphogenesis. Using EGFP miRNA sensors, we demonstrate that FMRP likely acts by regulating miR-276a RNA targeting rather than by modulating miRNA levels. Supporting this conclusion, miR-276a co-immunoprecipitated with FMRP and this association was dependent on the FMRP KH domains. By testing putative targets of the FMRP-miR-276a regulatory axis, we identified nejire (nej) as a FMRP-associated mRNA and, using EGFP reporters, showed that the nej 3′ UTR is a target of miR-276a in vivo. Genetic analysis places nej downstream of the FMRP-miR-276a pathway in regulating dendrite patterning. Together, our findings support a model in which FMRP facilitates miR-276a-mediated control of nej for proper dendrite space filling morphology, and shed light on miRNA-dependent dendrite developmental pathology of Fragile X syndrome.

Dermatophagoides farinae microRNAs released to external environments via exosomes regulate inflammation-related gene expression in human bronchial epithelial cells

“…Previous studies have shown that the expression level of miR-1 in peripheral blood of children suffering from acute-stage asthma positively correlated with interferon (IFN)-g expression and negatively correlated with disease severity (21). The metabolic balance of miR-276 determined the reproductive cycle of mosquitoes and the development of Plasmodium falciparum (22), and miR-276a played an important role in fragile X mental retardation protein (FMRP)-mediated spatial filling dendritic morphogenesis in Drosophila melanogaster (2). However, our study reported for the first time that miR-276-3p was highly expressed in the in-vitro model of allergic disease.…”

“…House dust mites (HDMs) are one of the most important and most common indoor allergen sources worldwide that lead to asthma and other respiratory allergic diseases (1), and Dermatophagoides farinae (DFA) and D. pteronyssinus (DPT), two common species of HDMs, are widely prevalent in temperate and tropical regions (2,3). It is estimated that 65 to 130 million people worldwide are affected by HDMs allergy (3).…”