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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Nature Publishing Group
2021-04-01
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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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id | doaj.art-cd7979eed9cd40ff9e69c456425eaefd |
institution | Directory Open Access Journal |
issn | 2041-4889 |
language | English |
last_indexed | 2024-12-20T13:28:36Z |
publishDate | 2021-04-01 |
publisher | Nature Publishing Group |
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series | Cell Death and Disease |
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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