Ji Baohu, Kim Minjung, Higa Kerin K, Zhou Xianjin
Department of Psychiatry, University of California, San Diego, California.
Am J Med Genet B Neuropsychiatr Genet. 2015 Jun;168B(4):284-95. doi: 10.1002/ajmg.b.32311. Epub 2015 May 5.
The t(1,11) chromosome translocation co-segregates with major psychiatric disorders in a large Scottish family. The translocation disrupts the DISC1and Boymaw (DISC1FP1) genes on chromosomes 1 and 11, respectively. After translocation, two fusion genes are generated. Our recent studies found that the DISC1-Boymaw fusion protein is localized in mitochondria and inhibits oxidoreductase activity, rRNA expression, and protein translation. Mice carrying the DISC1-Boymaw fusion genes display intermediate behavioral phenotypes related to major psychiatric disorders. Here, we report that the Boymaw gene may encode a small protein predominantly localized in mitochondria. The Boymaw protein inhibits oxidoreductase activity, rRNA expression, and protein translation in the same way as the DISC1-Boymaw fusion protein. Interestingly, Boymaw expression is up-regulated by different stressors at RNA and/or protein translational levels. In addition, we found that Boymaw RNA expression is significantly increased in the postmortem brains of patients with major psychiatric disorders. Our studies therefore suggest that the Boymaw gene could potentially be a susceptibility gene for major psychiatric disorders in both the Scottish t(1,11) family and the general population of patients.
在一个大型苏格兰家族中,t(1,11)染色体易位与主要精神疾病共分离。该易位分别破坏了1号和11号染色体上的DISC1和Boymaw(DISC1FP1)基因。易位后,产生了两个融合基因。我们最近的研究发现,DISC1 - Boymaw融合蛋白定位于线粒体中,并抑制氧化还原酶活性、rRNA表达和蛋白质翻译。携带DISC1 - Boymaw融合基因的小鼠表现出与主要精神疾病相关的中间行为表型。在此,我们报告Boymaw基因可能编码一种主要定位于线粒体的小蛋白。Boymaw蛋白以与DISC1 - Boymaw融合蛋白相同的方式抑制氧化还原酶活性、rRNA表达和蛋白质翻译。有趣的是,Boymaw的表达在RNA和/或蛋白质翻译水平上受到不同应激源的上调。此外,我们发现,在患有主要精神疾病患者的死后大脑中,Boymaw RNA表达显著增加。因此,我们的研究表明,Boymaw基因可能是苏格兰t(1,11)家族和一般精神疾病患者群体中主要精神疾病的一个易感基因。