title: RNA-binding protein hoip accelerates polyQ-induced neurodegeneration in Drosophila.
abstract: Abnormal polyglutamine (polyQ) expansion in the N-terminal domain of the human androgen receptor (hAR) is known to cause spinobulbar muscular atrophy (SBMA), a hereditary human neurodegenerative disorder. To explore the molecular mechanisms of neurodegeneration in SBMA, we genetically screened modulators of neurodegeneration in a Drosophila SBMA experimental model system. We identified hoip as an accelerator of polyQ-induced neurodegeneration. We found that hoip forms a complex with 18s rRNA together nop56 and nop5 proteins, whose human homologs are known to form a snoRNP complex involved in ribosomal RNA processing. Significantly, the levels of mutant polyQ-hAR were up-regulated in a mutant line overexpressing hoip. Consistently, severe neurodegeneration phenotype (rough eye) was also observed in both nop56 and nop5 overexpression mutant lines. These findings suggest that the process of neurodegeneration induced by abnormal polyQ expansion in the hAR may be regulated by the activity of snoRNP complex.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Murata
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.forename: Shun
authors.initials: S
authors.lastname: Sawatsubashi
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamagata
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanabe
authors.forename: Sally
authors.initials: S
authors.lastname: Fujiyama
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsukawa
authors.forename: Alexander
authors.initials: A
authors.lastname: Kouzmenko
authors.forename: Takashi
authors.initials: T
authors.lastname: Furutani
authors.forename: Erina
authors.initials: E
authors.lastname: Kuranaga
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004330:Drosophila / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000648:ultrastructure; D017344:Genes, Insect; D020966:Muscular Disorders, Atrophic / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen; D014162:Transfection
chemical_list: C410798:AR protein, human; D029721:Drosophila Proteins; D010455:Peptides; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; C533658:hoip protein, Drosophila; C097188:polyglutamine