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

Cell Death Dis. 2021 Apr 6;12(4):363. doi: 10.1038/s41419-021-03649-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DEAD-box RNA Helicases / metabolism*
  • Down-Regulation
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental / physiology*
  • Janus Kinases / metabolism*
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / physiology
  • Transcription Factors / metabolism


  • Drosophila Proteins
  • STAT Transcription Factors
  • Transcription Factors
  • Janus Kinases
  • DEAD-box RNA Helicases
  • maheshvara protein, Drosophila