Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, New York, NY, 10461, USA.
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.
马heshvara（mahe）是一种在分类群中广泛保守的 RNA 解旋酶，它调节果蝇中的 Notch 信号转导和神经元发育。为了鉴定由 mahe 调控的新组件，对异位 mahe 进行了转录组谱分析，结果显示 Notch 信号通路组件如 upd1、upd2、upd3 和 socs36E 的显著上调。此外，mahe 功能丧失突变体以及通过 RNAi 降低 mahe 水平时这些通路组件的显著下调，支持并加强了我们的转录组数据。平行地，我们观察到 mahe 在光感受器神经元中诱导了 caspase 依赖性细胞凋亡，而 JAK/STAT 通路组件显著调节了这种表型。RNA 免疫沉淀揭示了 Mahe 与 JAK/STAT 酪氨酸激酶 hopscotch（hop）转录本共沉淀的存在，这最终导致 hop 转录本的稳定和升高。此外，我们还观察到下游转录因子 Stat92E 的活性激增，这表明 JAK/STAT 信号的激活，而这反过来又通过 hid 的上调导致细胞凋亡。总之，我们的数据提供了 RNA 解旋酶 Maheshvara 对 JAK/STAT 通路的新调控，最终促进了细胞凋亡。
