title: Regulation of Notch Signaling by an Evolutionary Conserved DEAD Box RNA Helicase, Maheshvara in Drosophila melanogaster.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India.
authors.forename: Satya
authors.initials: S
authors.lastname: Surabhi
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India.
authors.forename: Bipin K
authors.initials: BK
authors.lastname: Tripathi
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India.
authors.forename: Bhawana
authors.initials: B
authors.lastname: Maurya
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Bhaskar
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India.
authors.forename: Ashim
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India mousumi_mutsuddi@yahoo.com mousumi@bhu.ac.in.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Mutsuddi
mesh_terms: D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014921:Wings, Animal / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D051155:Wnt1 Protein; C066381:ct protein, Drosophila; C074622:wg protein, Drosophila; D053487:DEAD-box RNA Helicases
keywords: DEAD box helicase; Drosophila; Notch signaling; RNA helicase; RNA-binding protein