A stress-responsive miRNA regulates BMP signaling to maintain tissue homeostasis

Adult organisms must sense, respond, and adapt to environmental fluctuations. In high-turnover tissues such as the intestine, these adaptive responses require rapid changes in gene expression that, in turn, likely involve post-transcriptional gene control. However, intestinal tissue specific microRNA mediated regulatory pathways remain unexplored. Here we report the role of an intestinal specific microRNA, miR-958, that non-cell autonomously regulates stem cell numbers during tissue homeostasis and regeneration in the Drosophila adult midgut. We identify its downstream target cabut, the Drosophila ortholog of mammalian KLF10/11 transcription factors, which mediates this miR-958 function by promoting paracrine enterocyte-to-stem cell BMP signaling. We also show that mature miR-958 levels transiently decrease in response to stress, and that this decrease is required for proper stem cell expansion during tissue regeneration. In summary, we have identified a novel post-transcriptional mechanism that modulates BMP signaling activity within Drosophila adult intestinal tissue both during normal homeostasis as well as tissue regeneration to regulate intestinal stem cell numbers. We compared microRNA read counts in small RNA libraries prepared from intestinal tissue and remaining "carcass" tissue from wildtype adult male Drosophila melanogaster. Analysis compared three intstinal samples to two carcass samples.