title: Altered translational repression of an RNA-binding protein, Elav by AOA2-causative Senataxin mutation.
abstract: Mutations in Senataxin (SETX) gene causes two types of neurological disorders, Amyotrophic Lateral Sclerosis (ALS4) and Ataxia with Oculomotor Apraxia type 2 (AOA2). Recent studies in cultured cells suggest that SETX plays a crucial role at the interface of transcription and the DNA damage response. Whether SETX can alter translational of specific RNA is not known. In this study, we report that expressing AOA2-causative truncated form of human SETX in Drosophila neurons alters the development of neuromuscular junction (NMJ) synapses. Interestingly, we found that expressing this truncated form of SETX in Drosophila muscles resulted in an alteration of translational repression of an RNA-binding protein, Embryonic Lethal Abnormal Vision (Elav). Elav is transcribed in all tissues but remains translationally repressed except in neurons. Thus, our data suggest that an altered repression profile of RNA by SETX mutants could be one of the mechanisms underlying ALS4 or AOA2 pathogenesis.
authors.affiliation: Department of Biological Sciences, Laboratory of Neurogenetics, Indian Institute of Science Education and Research (IISER) Bhopal, Bhouri, Bhopal, Madhya Pradesh, India, 462 066.
authors.forename: Saumitra Dey
authors.identifier: 0000-0001-8828-4551
authors.initials: SD
authors.lastname: Choudhury
authors.affiliation: Department of Biological Sciences, Laboratory of Neurogenetics, Indian Institute of Science Education and Research (IISER) Bhopal, Bhouri, Bhopal, Madhya Pradesh, India, 462 066.
authors.forename: Ancy
authors.initials: A
authors.lastname: Vs
authors.affiliation: Department of Biological Sciences, Laboratory of Neurogenetics, Indian Institute of Science Education and Research (IISER) Bhopal, Bhouri, Bhopal, Madhya Pradesh, India, 462 066.
authors.forename: Zeeshan
authors.identifier: 0000-0003-3416-2289
authors.initials: Z
authors.lastname: Mushtaq
authors.affiliation: Department of Biological Sciences, Laboratory of Neurogenetics, Indian Institute of Science Education and Research (IISER) Bhopal, Bhouri, Bhopal, Madhya Pradesh, India, 462 066.
authors.forename: Vimlesh
authors.identifier: 0000-0003-2206-4905
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D004265:DNA Helicases; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D051959:ELAV Proteins / Q000235:genetics* / Q000378:metabolism; D064251:Multifunctional Enzymes; D009154:Mutation; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000235:genetics* / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000151:congenital* / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D051959:ELAV Proteins; C498009:ELAV protein, Drosophila; D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases
keywords: elav; phospho-MAD; senataxin; synapse; translational repression