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

Biosci Biotechnol Biochem. 2008 Sep;72(9):2255-61. doi: 10.1271/bbb.70829. Epub 2008 Sep 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Disease Models, Animal
  • Drosophila / cytology
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Eye / metabolism
  • Eye / ultrastructure
  • Genes, Insect*
  • Muscular Disorders, Atrophic / genetics
  • Muscular Disorders, Atrophic / metabolism
  • Mutation
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism*
  • Peptides / metabolism*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Receptors, Androgen
  • Transfection

Substances

  • AR protein, human
  • Drosophila Proteins
  • Peptides
  • RNA-Binding Proteins
  • Receptors, Androgen
  • hoip protein, Drosophila
  • polyglutamine