A polycistronic locus encodes both a tumor-suppressive microRNA and a long non-coding RNA regulating testis...

The impact of non-coding RNAs on stem cell biology and differentiation processes is an important and incompletely understood area of research. Using the testes of Drosophila melanogaster as a valuable system for investigating these processes, we identified a polycistronic locus from which two non-coding transcripts, miR-317 and the long non-coding RNA (lncRNA) Peony, are produced, with alternative polyadenylation implicated in regulation of their differential expression levels. We report here that each transcript has a distinct role in Drosophila testes; the increased expression of Peony results in the disruption of the muscle sheath covering the testis, and the absence of miR-317 leads to the emergence of germ-cell tumors in developing flies. The deficiency of miR-317 increases Notch signaling activity in somatic cyst cells, upregulates multiple predicted targets of miR-317, and drives germline tumorigenesis. This work implicates miR-317 as a tumor suppressor that modulates Notch signaling strength and suggests alternative polyadenylation as a novel mechanism for regulation of miRNA expression.