Institute for Systems Biology, Jianghan University, Wuhan, 430056 Hubei, China.
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, 300134 Tianjin, China.
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4435-4440. doi: 10.1073/pnas.1719206115. Epub 2018 Apr 9.
Cells have developed regulatory mechanisms that underlie flagellar assembly and maintenance, including the transcriptional regulation of flagellar genes, an initial step for making flagella. Although transcriptional regulation of flagellar gene expression is required for flagellar assembly in , no transcription factor that regulates the transcription of flagellar genes has been identified. We report that X chromosome-associated protein 5 (XAP5) acts as a transcription factor to regulate flagellar assembly in While XAP5 proteins are evolutionarily conserved across diverse organisms and play vital roles in diverse biological processes, nothing is known about the biochemical function of any member of this important protein family. Our data show that loss of XAP5 leads to defects in flagellar assembly. Posttranslational modifications of XAP5 track flagellar length during flagellar assembly, suggesting that cells possess a feedback system that modulates modifications to XAP5. Notably, XAP5 regulates flagellar gene expression via directly binding to a motif containing a CTGGGGTG-core. Furthermore, recruitment of RNA polymerase II (Pol II) machinery for transcriptional activation depends on the activities of XAP5. Our data demonstrate that, through recruitment of Pol II, XAP5 defines a class of transcription factors for transcriptional regulation of ciliary genes. This work provides insights into the biochemical function of the XAP5 family and the fundamental biology of the flagellar assembly, which enhance our understanding of the signaling and functions of flagella.
细胞已经开发出了基础性的调控机制，以实现鞭毛的组装和维护，包括鞭毛基因的转录调控，这是制造鞭毛的初始步骤。尽管转录调控是鞭毛组装所必需的，但尚未鉴定出调节鞭毛基因转录的转录因子。我们报告称，X 染色体相关蛋白 5（XAP5）作为转录因子在 中调节鞭毛组装。虽然 XAP5 蛋白在不同的生物体中是进化保守的，并且在各种生物学过程中发挥着重要作用，但对于这个重要蛋白家族的任何成员的生化功能都一无所知。我们的数据表明，XAP5 的缺失会导致鞭毛组装缺陷。XAP5 的翻译后修饰在鞭毛组装过程中跟踪鞭毛的长度，这表明细胞具有一种反馈系统，可以调节 XAP5 的修饰。值得注意的是，XAP5 通过直接结合含有 CTGGGGTG 核心的基序来调节鞭毛基因的表达。此外，转录激活所需的 RNA 聚合酶 II（Pol II）机制的募集依赖于 XAP5 的活性。我们的数据表明，通过 Pol II 的募集，XAP5 定义了一类转录因子，用于对纤毛基因进行转录调控。这项工作深入了解了 XAP5 家族的生化功能和鞭毛组装的基础生物学，增强了我们对鞭毛信号和功能的理解。
