Rbfox1 and mir-33 regulate pleiotropic roles of JAK/STAT signalling during adult myogenesis in Drosophila melanogaster

Abstract

The JAK/STAT pathway is a conserved metazoan signal transduction system with roles in regulating growth, stem cells, and immune responses. Although its components are ubiquitously expressed during development, JAK/STAT signalling exerts cell-specific effects through mechanisms largely unknown. Here, we demonstrate that cell-specific effects of JAK/STAT signalling could be realised through post-transcriptional regulation. We show that JAK/STAT signalling in early adult myogenesis is critical for the patterning of the dorsal longitudinal muscles in Drosophila melanogaster. RNA-binding Fox protein 1 (Rbfox1) and the microRNA mir-33 regulate the transcript stability of Signal-transducer and activator of transcription protein at 92E (Stat92E), which encodes the sole Drosophila STAT orthologue. Moreover, Rbfox1 also controls the alternative splicing of Stat92E and its key downstream effector, Zn finger homeodomain 1 (zfh1). The coupling of Rbfox1 with Stat92E function, during early adult myogenesis, not only allows maintenance of stemness, but also mediates filamentous actin dynamics, and prevents apoptosis in myoblasts via some other Stat92E target genes. Given that the functions of the JAK/STAT pathway in cell proliferation and survival are conserved between Drosophila and vertebrates, our report presents a novel example for the context-dependant regulation of the developmental role of an important signalling pathway.