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bioRxiv · 10.1101/2024.10.10.617551

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

Carney, T. D.·Shcherbata, H. R.
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Abstract

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. Our findings establish miR-317 as a tumor suppressor controlling Notch signaling strength and uncover alternative polyadenylation as an unrecognized mechanism governing miRNA expression.

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Carney, T. D., Shcherbata, H. R.. 2024-10-10. Tumor suppressor miR-317 and lncRNA Peony are expressed from a polycistronic non-coding RNA locus that regulates germline differentiation and testis morphology. https://doi.org/10.1101/2024.10.10.617551

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