RNA-binding protein hoip accelerates polyQ-induced neurodegeneration in Drosophila
RNA-binding protein hoip accelerates polyQ-induced neurodegeneration in Drosophila
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DOI：
10.1271/bbb.70829
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发表时间：
2008-09-01
影响因子：
1.6
通讯作者：
Kato, Shigeaki
中科院分区：
文献类型：
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作者：
Murata, Takuya;Suzuki, Eriko;Kato, Shigeaki
已知人雄激素受体（hAR）N-末端结构域中的异常聚谷氨酰胺（polyQ）扩增可引起脊髓延髓肌萎缩症（SBMA），这是一种遗传性人类神经退行性疾病。为了探索SBMA神经退行性变的分子机制，我们在果蝇SBMA实验模型系统中遗传筛选了神经退行性变的调节剂。我们将hoip鉴定为polyQ诱导的神经变性的加速剂。我们发现hoip与nop 56和nop 5蛋白一起与18 s rRNA形成复合物，已知nop 56和nop 5蛋白的人类同系物形成参与核糖体RNA加工的snoRNP复合物。值得注意的是，突变体polyQ-hAR的水平在过表达hoip的突变体系中上调。一致地，在nop 56和nop 5过表达突变株中也观察到严重的神经变性表型（粗糙眼）。这些发现表明，hAR中异常polyQ扩增诱导的神经变性过程可能受到snoRNP复合物活性的调节。
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.