The bantam microRNA is associated with drosophila fragile X mental retardation protein and regulates the fate of germline stem cells

Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP). We have previously demonstrated that dFmr1, the Drosophila ortholog of the fragile X mental retardation 1 gene, plays a role in the proper maintenance of germline stem cells in Drosophila ovary; however, the molecular mechanism behind this remains elusive. In this study, we used an immunoprecipitation assay to reveal that specific microRNAs (miRNAs), particularly the bantam miRNA (bantam), are physically associated with dFmrp in ovary. We show that, like dFmr1, bantam is not only required for repressing primordial germ cell differentiation, it also functions as an extrinsic factor for germline stem cell maintenance. Furthermore, we find that bantam genetically interacts with dFmr1 to regulate the fate of germline stem cells. Collectively, our results support the notion that the FMRP-mediated translation pathway functions through specific miRNAs to control stem cell regulation.
Author Summary Fragile X syndrome, the most common cause of inherited mental retardation, results from the loss of functional Fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein and is known to bind to specific mRNAs and regulate their translation both in vitro and in vivo. Previous studies have suggested that FMRP is one component of the miRNA pathway involved in miRNA-mediated translational control. In the past we found that, as a translational regulator, dFmrp can modulate the proliferation and fate specification of stem cells in Drosophila, likely via the miRNA pathway. However, whether dFmrp could use specific miRNAs to regulate the fate of GSCs has remained unclear. Here, we show that dFmrp is associated with specific microRNAs (miRNAs), including the bantam miRNA, in Drosophila ovary. Furthermore, we show that bantam genetically interacts with dFmr1 to regulate the fate of GSCs. Our findings imply that FMRP could utilize specific miRNAs to regulate the translation of its mRNA targets.