MicroRNA miR-274-5p Suppresses Found-in-Neurons Associated with Melanotic Mass Formation and Developmental Growth in Drosophila

SIMPLE SUMMARY: In animals, including humans and flies, blood cells play crucial roles in various biological processes, such as immune response and normal development. The abnormal regulation of hematopoiesis in flies results in the formation of melanotic masses, which are also known as melanotic tumors. However, the detailed mechanisms underlying this process are not fully understood. In this study, we found that the upregulation of miR-274-5p, a small non-coding RNA, activates the JNK and JAK/STAT signaling pathways by suppressing the expression of found-in-neurons (fne) encoding an RNA-binding protein in flies. This regulation controls the formation of melanotic masses and developmental growth. Overall, our findings provide valuable insights into melanotic mass formation and developmental growth as well as the regulatory network of the JNK and JAK/STAT signaling pathways. ABSTRACT: The hematopoietic system plays a crucial role in immune defense response and normal development, and it is regulated by various factors from other tissues. The dysregulation of hematopoiesis is associated with melanotic mass formation; however, the molecular mechanisms underlying this process are poorly understood. Here, we observed that the overexpression of miR-274 in the fat body resulted in the formation of melanotic masses. Moreover, abnormal activation of the JNK and JAK/STAT signaling pathways was linked to these consequences. In addition to this defect, miR-274 overexpression in the larval fat body decreased the total tissue size, leading to a reduction in body weight. miR-274-5p was found to directly suppress the expression of found-in-neurons (fne), which encodes an RNA-binding protein. Similar to the effects of miR-274 overexpression, fne depletion led to melanotic mass formation and growth reduction. Collectively, miR-274 plays a regulatory role in the fne–JNK signaling axis in melanotic mass formation and growth control.