RNA-binding protein hoip accelerates polyQ-induced neurodegeneration in Drosophila

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2008-09, Vol.72 (9), p.2255-2261
• Main Authors: Murata, T.(Tokyo Univ. (Japan)), Suzuki, E, Ito, S, Sawatsubashi, S, Zhao, Y, Yamagata, K, Tanabe, M, Fujiyama, S, Kimura, S, Ueda, T, Matsukawa, H, Kouzmenko, A, Furutani, T, Kuranaga, E, Miura, M, Takeyama, K, Kato, S
• Format: Article
• Language: English
• Subjects: androgen receptor; ANDROGENE; ANDROGENOS; ANDROGENS; Animals; Animals, Genetically Modified; Biological and medical sciences; Cells, Cultured; Disease Models, Animal; DROSOPHILA; Drosophila - cytology; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; ENFERMEDADES NEUROMUSCULARES; Eye - metabolism; Eye - ultrastructure; Fundamental and applied biological sciences. Psychology; GENERO HUMANO; Genes, Insect; GENETIC DISORDERS; GENRE HUMAIN; HORMONE RECEPTORS; MALADIE NEUROMUSCULAIRE; MANKIND; Muscular Disorders, Atrophic - genetics; Muscular Disorders, Atrophic - metabolism; Mutation; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; neurodegeneration; NEUROMUSCULAR DISEASES; Peptides - metabolism; RECEPTEUR D'HORMONE; RECEPTORES DE HORMONAS; Receptors, Androgen; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; rRNA processing; spinobulbar muscular atrophy; Transfection; TRASTORNOS GENETICOS; TROUBLE GENETIQUE
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.70829

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.