Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster

Abstract

AbstractMaheshvara (mahe), an RNA helicase that is widely conserved across taxa, regulates Notch signaling and neuronal development inDrosophila. In order to identify novel components regulated bymahe, transcriptome profiling of ectopicmahewas carried out and this revealed striking upregulation of JAK/STAT pathway components likeupd1,upd2,upd3, andsocs36E. Further, significant downregulation of the pathway components inmaheloss-of-function mutant as well as upon lowering the level ofmahebyRNAi, supported and strengthened our transcriptome data. Parallelly, we observed thatmahe, induced caspase-dependent apoptosis in photoreceptor neurons, and this phenotype was significantly modulated by JAK/STAT pathway components. RNA immunoprecipitation unveiled the presence of JAK/STAT tyrosine kinasehopscotch(hop) transcripts in the complex immunoprecipitated with Mahe, which ultimately resulted in stabilization and elevation ofhoptranscripts. Additionally, we also observed the surge in activity of downstream transcription factor Stat92E, which is indicative of activation of the JAK/STAT signaling, and this in turn led to apoptosis via upregulation ofhid. Taken together, our data provide a novel regulation of JAK/STAT pathway by RNA helicase Maheshvara, which ultimately promotes apoptosis.