Browsing by Author "Satya Surabhi"

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DLin52 is crucial for dE2F and dRBF mediated transcriptional regulation of pro-apoptotic gene hid
(Elsevier, 2014) Pradeep Kumar Bhaskar; Satya Surabhi; Bipin Kumar Tripathi; Ashim Mukherjee; Mousumi Mutsuddi
Drosophila lin52 (dlin52) is a member of Myb transcription regulator complex and it shows a dynamic pattern of expression in all Drosophila tissues. Myb complex functions to activate or repress transcription in a site-specific manner; however, the detailed mechanism is yet to be clearly understood. Members of the Drosophila melanogaster Myb-MuvB/dREAM complex have been known to regulate expression of a wide range of genes including those involved in regulating apoptosis. E2F and its corepressor RBF also belong to this complex and together they regulate expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. In the present study, we examined whether the depletion of dlin52 in developing photoreceptor neurons results in enhanced apoptosis and disorganisation of the ommatidia. Strikingly, we found that dLin52 is essential for transcriptional repression of the pro-apoptotic gene, hid; decrease in dlin52 levels led to dramatic induction of hid and apoptosis in eye-antennal discs. Reduction of Rpd3 (HDAC1), another member of the dREAM complex, also led to marginal upregulation of Hid. In addition, we also demonstrated that an optimum level of dLin52 is needed for dE2F1/2 activity on the hid promoter. dlin52 cooperates with dRBF and dE2F1/2 for recruitment of repressor complex on the hid promoter. Preliminary data indicate that Rpd3/HDAC1 also contributes to hid repression. Based on the findings, we conclude that dLin52 functions as a co-factor and modulates activity of members of dMyb/dREAM complex at hid promoter, thus regulating apoptosis by repressing this pro-apoptotic gene in the developing Drosophila eye. © 2014 Elsevier B.V.
Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
(Springer Nature, 2021) Bhawana Maurya; Satya Surabhi; Rituparna Das; Pranjali Pandey; Ashim Mukherjee; Mousumi Mutsuddi
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. © 2021, The Author(s).
Maheshvara, a Conserved RNA Helicase, Regulates Notch Signaling in Drosophila melanogaster
(Springer, 2020) Bhawana Maurya; Satya Surabhi; Ashim Mukherjee; Mousumi Mutsuddi
Gene expression is regulated at multiple steps after generation of primary RNA transcripts, including mRNA processing, stability, and transport, along with co- and post-transcriptional regulation. These processes are controlled via the involvement of a multitude of RNA binding proteins (RBPs). Innumerable human diseases have been associated with altered expression of RNA binding proteins. In this chapter we have focused on Maheshvara (mahe) which encodes a putative DEAD box RNA helicase protein in Drosophila. We have recently reported that mahe plays an important role in regulation of Notch signaling. Fine tuning of Notch signaling is required at multiple steps and it’s misregulation leads to a variety of human diseases. Additionally, mutation in DDX59, a human homolog of mahe results in broad neurological phenotypes associated with orofaciodigital syndrome. Drosophila mahe mutants show abnormal peripheral and central nervous system development that resemble neuropathology of patients having mutation in DDX59 gene. This chapter will help in advancing the knowledge as to how mahe regulates Notch signaling and nervous system development. © 2020, Springer Nature Switzerland AG.
Regulation of notch signaling by an evolutionary conserved DEAD box RNA helicase, maheshvara in drosophila melanogaster
(Genetics, 2015) Satya Surabhi; Bipin K. Tripathi; Bhawana Maurya; Pradeep K. Bhaskar; Ashim Mukherjee; Mousumi Mutsuddi
Notch signaling is an evolutionary conserved process that influences cell fate determination, cell proliferation, and cell death in a context-dependent manner. Notch signaling is fine-tuned at multiple levels and misregulation of Notch has been implicated in a variety of human diseases. We have characterized maheshvara (mahe), a novel gene in Drosophila melanogaster that encodes a putative DEAD box protein that is highly conserved across taxa and belongs to the largest group of RNA helicase. A dynamic pattern of mahe expression along with the maternal accumulation of its transcripts is seen during early stages of embryogenesis. In addition, a strong expression is also seen in the developing nervous system. Ectopic expression of mahe in a wide range of tissues during development results in a variety of defects, many of which resemble a typical Notch loss-of-function phenotype. We illustrate that ectopic expression of mahe in the wing imaginal discs leads to loss of Notch targets, Cut and Wingless. Interestingly, Notch protein levels are also lowered, whereas no obvious change is seen in the levels of Notch transcripts. In addition, mahe overexpression can significantly rescue ectopic Notch-mediated proliferation of eye tissue. Further, we illustrate that mahe genetically interacts with Notch and its cytoplasmic regulator deltex in trans-heterozygous combination. Coexpression of Deltex and Mahe at the dorso-ventral boundary results in a wing-nicking phenotype and a more pronounced loss of Notch target Cut. Taken together we report identification of a novel evolutionary conserved RNA helicase mahe, which plays a vital role in regulation of Notch signaling. © 2015 by the Genetics Society of America.
The expanding role of RNA-binding proteins in neurodegeneration
(Springer Singapore, 2019) Bhawana Maurya; Satya Surabhi; Pranjali Pandey; Ashim Mukherjee; Mousumi Mutsuddi
In eukaryotic cells, gene expression is regulated at various levels after generation of a primary RNA transcript, including mRNA processing, transport, stability, and co-and post-transcriptional regulation. These processes are tightly controlled by the action of a multitude of RNA-binding proteins (RBPs). As soon as an RNA is transcribed, RBPs regulate the RNA at every step, starting from processing up to its final degradation. RNA processing plays a fundamental role in regulating multiple events during nervous system development. So far, RBPs have been shown to be important for neurogenesis, neurite outgrowth, maintaining neural stem cells, synapse formation, and plasticity. In addition, studies have depicted that several neurological diseases are associated with deregulated genes involved in RNA metabolism. Moreover, alterations in RNA-binding proteins are associated with many neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), fragile X syndrome (FXS), spinal muscular atrophy (SMA), and many others. Drosophila has been one of the best model organisms to understand neurodegeneration at the molecular level. In this chapter, we report the use of Drosophila in comprehending recent advances that link RBPs with neurodegenerative processes. This will help in advancing our knowledge as to how RBP dysfunction contributes to neurological diseases. © Springer Nature Singapore Pte Ltd. 2019.
The RNA binding KH domain of Spoonbill depletes pathogenic non-coding spinocerebellar ataxia 8 transcripts and suppresses neurodegeneration in Drosophila
(Elsevier B.V., 2016) Bipin K. Tripathi; Satya Surabhi; Pradeep K. Bhaskar; Ashim Mukherjee; Mousumi Mutsuddi
Spinocerebellar ataxia 8 (SCA8) pathogenesis is a resultant of gain-of-function machinery that primarily results at the RNA level. It has been reported that expanded non-coding CTG trinucleotide repeat in the ATXN8OS transcripts leads to SCA8 coupled neurodegeneration. Targeted depletion of pathogenic SCA8 transcripts is a viable therapeutic approach. In this report we have focused on the suppression of toxic RNA gain-of-function associated with SCA8. We report suppression of SCA8 associated neurodegeneration by KH RNA binding domain of Spoonbill. KH domain suppresses pathogenic SCA8 associated phenotype in adult flies. Ectopic expression of KH domain leads to massive reduction in the number and size of SCA8 RNA foci. We show that Spoonbill interacts with toxic SCA8 transcripts via its KH domain and promotes its depletion. Till date, no attempts have been made for therapeutic intervention of SCA8 pathogenesis. Further characterization of Spoonbill KH domain may aid us in designing peptide based therapeutics for SCA8 associated neurodegeneration. © 2016 Elsevier B.V.