CTP synthase regulation by miR-975 controls cell proliferation and differentiation inDrosophila melanogaster

CTP synthase (CTPsyn) is an essential metabolic enzyme. As a key regulator of the nucleotide pool, the protein has been found to be elevated in cancer models. In many organisms, CTPsyn compartmentalizes into filaments termed cytoophidia. For D. melanogaster , it is only its Isoform C i.e. CTPsynIsoC which forms the structure. The fruit fly’s testis is home to somatic and germline stem cells. Both micro and macro-cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located and development is at its most rapid. Here, we report that CTPsynIsoC overexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately one-third of like-genotyped males. Immunostaining shows that the cause of this tumour-like phenotype is most likely due to increased numbers of both germline cells and spermatocytes. We also report that under conditions whereby miR-975 is overexpressed, greater incidences of the same bulged-phenotype coincides with induced upregulation of CTPsynIsoC. However, RT-qPCR assays reveal that either overexpression genotype provokes a differential response in expression of a number of genes concurrently associated with CTPsyn and cancer, showing that the pathways CTPsynIsoC affect and miR-975 regulate may be completely independent of each other. This study presents the first instance of consequences of miRNA-asserted regulation upon CTPsyn in D. melanogaster , and further reaffirms the enzyme’s close ties to cancer and carcinogenesis.