Tumor suppressor miR-317 and lncRNA Peony are expressed from a polycistronic non-coding RNA locus that regulates germline differentiation and testis morphology

This research focuses on investigating the impact of non-coding RNAs on stem cell biology and differentiation processes. We found that miR-317 plays a role in germline stem cell progeny differentiation. miR-317 and its neighbor, the lncRNA Peony, originate and are co-expressed from a singular polycistronic non-coding RNA locus. Alternative polyadenylation is implicated in regulation of their differential expression. While the increased expression of the lncRNA Peony results in the disruption of the muscle sheath covering the testis, the absence of miR-317 leads to the emergence of germline tumors in young flies. The deficiency of miR-317 increases Notch signaling activity in the somatic cyst cells, which drives germline tumorigenesis. Germline tumors also arise from upregulation of several predicted targets of miR-317, among which are regulators of the Notch pathway. This implicates miR-317 as a novel tumor suppressor that modulates Notch signaling strength.