X chromosome-linked intellectual disability protein PQBP1 associates with and regulates the translation of specific mRNAs
X chromosome-linked intellectual disability protein PQBP1 associates with and regulates the translation of specific mRNAs
复制标题
DOI：
10.1093/hmg/ddv191
复制
发表时间：
2015-08-15
影响因子：
3.5
通讯作者：
Han, Junhai
中科院分区：
文献类型：
--
作者：
Wan, Didi;Zhang, Zi Chao;Han, Junhai
X染色体连锁智力障碍是一种常见的发育障碍，聚谷氨酰胺结合蛋白1(PQBP1)基因的突变与这种疾病有关。PQBP1除了作为剪接因子存在于细胞核外，还存在于细胞质RNA颗粒中，与RNA结合蛋白结合。然而，细胞质PQBP1的作用在很大程度上是未知的。在这里，我们发现PQBP1的果蝇同源物(DPQBP1)存在于光感受器细胞的细胞质中，它的丢失导致横纹状体形态发生缺陷，这是由于Chaoptin翻译受损所致。我们还发现dPQBP1通过与dFMR1相互作用来调节mRNA的翻译，dFMR1与特定的mRNAs结合，并促进它们组装成翻译核糖体，这是人类PQBP1和FMRP保守的功能。我们的发现揭示了PQBP1在mRNA翻译中的保守功能，并为研究Renpenning综合征的发病机制提供了分子基础。
X chromosome-linked intellectual disability is acommondevelopmental disorder, and mutations of the polyglutamine-binding protein 1 (PQBP1) gene have been linked to this disease. In addition to existing in the nucleus as a splicing factor, PQBP1 is also found in cytoplasmic RNA granules, where it associates with RNA-binding proteins. However, the roles of cytoplasmic PQBP1 are largely unknown. Here, we show that the Drosophila homolog of PQBP1 (dPQBP1) is present in the cytoplasm of photoreceptor cells, and its loss results in defective rhabdomere morphogenesis, which is due to impaired Chaoptin translation. We also show that dPQBP1 regulates mRNA translation by interacting with dFMR1, which binds to specific mRNAs and facilitates their assembly into translating ribosomes, a function that is conserved for human PQBP1 and FMRP. Our findings reveal the conserved function of PQBP1 in mRNA translation and provide molecular insights into the pathogenic mechanisms underlying Renpenning syndrome.