Chennathukuzhi Vargheese, Morales Carlos R, El-Alfy Mohamed, Hecht Norman B
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6142, USA.
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15566-71. doi: 10.1073/pnas.2536695100. Epub 2003 Dec 12.
Testis brain RNA-binding protein (TB-RBP), the mouse orthologue of the human protein Translin, is a widely expressed and highly conserved protein with proposed functions in chromosomal translocations, mitotic cell division, and mRNA transport, stabilization, and storage. Targeted inactivation of TB-RBP leads to abnormalities in fertility and behavior. A testis-enriched kinesin KIF17b coimmunoprecipitates with TB-RBP in a RNA-protein complex containing specific cAMP-responsive element modulator (CREM)-regulated mRNAs. The specificity of this interaction is confirmed by in vivo RNA-protein crosslinking and transfections of hippocampal neurons. Combining in situ hybridization and immunohistochemistry at the electron microscope level, a temporally sequential dissociation of KIF17b and TB-RBP from specific mRNAs is detected with TB-RBP release coincident with the time of mRNA translation, indicating a separation of the processes of transport and translation. We conclude that KIF17b serves as a molecular motor component of a TB-RBP-mouse ribonucleoprotein complex transporting a group of specific CREM-regulated mRNAs in mammalian male postmeiotic germ cells. Because KIF17b has been reported to control CREM-dependent transcription in male germ cells by regulating the intracellular location of the transcriptional coactivator activator of CREM in testis, this indicates that one kinesin links the processes of transcription and transport of specific mRNAs in mammalian male germ cells.
睾丸脑RNA结合蛋白（TB-RBP）是人类转运蛋白（Translin）的小鼠同源物，是一种广泛表达且高度保守的蛋白质，在染色体易位、有丝分裂细胞分裂以及mRNA运输、稳定和储存方面具有特定功能。TB-RBP的靶向失活会导致生育能力和行为异常。一种在睾丸中高度富集的驱动蛋白KIF17b在一个包含特定环磷酸腺苷反应元件调节因子（CREM）调控的mRNA的RNA-蛋白质复合物中与TB-RBP共同免疫沉淀。体内RNA-蛋白质交联和海马神经元转染证实了这种相互作用的特异性。在电子显微镜水平结合原位杂交和免疫组织化学，检测到KIF17b和TB-RBP从特定mRNA上按时间顺序依次解离，TB-RBP的释放与mRNA翻译时间一致，这表明运输和翻译过程是分离的。我们得出结论，KIF17b作为TB-RBP-小鼠核糖核蛋白复合物的分子马达成分，在哺乳动物雄性减数分裂后生殖细胞中运输一组特定的CREM调控的mRNA。因为据报道KIF17b通过调节睾丸中CREM转录共激活因子激活剂的细胞内定位来控制雄性生殖细胞中CREM依赖的转录，这表明一种驱动蛋白连接了哺乳动物雄性生殖细胞中特定mRNA的转录和运输过程。
