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

Abstract

Maheshvara (mahe), an RNA helicase that is widely conserved across taxa, regulates Notch signaling and neuronal development in Drosophila. In order to identify novel components regulated by mahe, transcriptome profiling of ectopic mahe was carried out and this revealed striking upregulation of JAK/STAT pathway components like upd1, upd2, upd3, and socs36E. Further, significant downregulation of the pathway components in mahe loss-of-function mutant as well as upon lowering the level of mahe by RNAi, supported and strengthened our transcriptome data. Parallelly, we observed that mahe, 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 kinase hopscotch (hop) transcripts in the complex immunoprecipitated with Mahe, which ultimately resulted in stabilization and elevation of hop transcripts. 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 of hid. Taken together, our data provide a novel regulation of JAK/STAT pathway by RNA helicase Maheshvara, which ultimately promotes apoptosis.

Cloning of suppressor of cytokine signaling 7 from silkworm (Bombyx mori) and its response to the infection of Bombyx mori nucleopolyhedrovirus

“…In the insect model Drosophila melanogaster, only three SOCS genes exist that encodes respective homologues of mammalian SOCS5 (SOCS36E), SOCS6 (SOCS44A), and SOCS7 (SOCS16D) (Rawlings et al, 2004). SOCS36E regulates development in Drosophila via modulation of the JAK-STAT pathway, such as tissue regeneration (Jaiswal et al, 2023), neuron apoptosis (Maurya et al, 2021), oogenesis (Monahan & Starz-Gaiano, 2015) and stem cell competition and renewal (Amoyel et al, 2016), while the roles of the other two remain largely unknown. Interestingly, a recent report suggests the involvement of SOCS36E in Drosophila tolerance to the infection of Pseudomonas entomophila (Prakash et al, 2023), indicating Drosophila SOCS proteins may also participate in host immune defense responses.…”