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...

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Main Authors: Bhawana Maurya, Satya Surabhi, Rituparna Das, Pranjali Pandey, Ashim Mukherjee, Mousumi Mutsuddi
Format: Article
Language:English
Published: Nature Publishing Group 2021-04-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-021-03649-0
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author Bhawana Maurya
Satya Surabhi
Rituparna Das
Pranjali Pandey
Ashim Mukherjee
Mousumi Mutsuddi
author_facet Bhawana Maurya
Satya Surabhi
Rituparna Das
Pranjali Pandey
Ashim Mukherjee
Mousumi Mutsuddi
author_sort Bhawana Maurya
collection DOAJ
description 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.
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spelling doaj.art-cd7979eed9cd40ff9e69c456425eaefd2022-12-21T19:39:11ZengNature Publishing GroupCell Death and Disease2041-48892021-04-0112411410.1038/s41419-021-03649-0Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogasterBhawana Maurya0Satya Surabhi1Rituparna Das2Pranjali Pandey3Ashim Mukherjee4Mousumi Mutsuddi5Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu UniversityDepartment of Molecular and Human Genetics, Institute of Science, Banaras Hindu UniversityDepartment of Molecular and Human Genetics, Institute of Science, Banaras Hindu UniversityDepartment of Molecular and Human Genetics, Institute of Science, Banaras Hindu UniversityDepartment of Molecular and Human Genetics, Institute of Science, Banaras Hindu UniversityDepartment of Molecular and Human Genetics, Institute of Science, Banaras Hindu UniversityAbstract 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.https://doi.org/10.1038/s41419-021-03649-0
spellingShingle Bhawana Maurya
Satya Surabhi
Rituparna Das
Pranjali Pandey
Ashim Mukherjee
Mousumi Mutsuddi
Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
Cell Death and Disease
title Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
title_full Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
title_fullStr Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
title_full_unstemmed Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
title_short Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
title_sort maheshvara regulates jak stat signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in drosophila melanogaster
url https://doi.org/10.1038/s41419-021-03649-0
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