Röther Susanne, Strässer Katja
Gene Center and Laboratory of Molecular Biology, Department of Chemistry and Biochemistry, Ludwig Maximilians University of Munich, 81377 Munich, Germany.
Genes Dev. 2007 Jun 1;21(11):1409-21. doi: 10.1101/gad.428407.
Translation is a highly complex process that is regulated by a multitude of factors. Here, we show that the conserved kinase Ctk1 functions in translation by enhancing decoding fidelity. Ctk1 associates with translating ribosomes in vivo and is needed for efficient translation. Ctk1 phosphorylates Rps2, a protein of the small ribosomal subunit, on Ser 238. Importantly, Ctk1-depleted as well as rps2-S238A mutant cells show a defect in translation elongation through an increase in the frequency of miscoding. The role of Ctk1 in translation may be conserved as the mammalian homolog of Ctk1, CDK9, also associates with polysomes. Since Ctk1 interacts with the TREX (transcription and mRNA export) complex, which couples transcription to mRNA export, Ctk1/CDK9 might bind to correctly processed mRNPs during transcription and accompany the mRNP to the ribosomes in the cytoplasm, where Ctk1 enhances efficient and accurate translation of the mRNA.
翻译是一个高度复杂的过程,受到多种因素的调控。在此,我们表明保守的激酶Ctk1通过提高解码保真度在翻译过程中发挥作用。Ctk1在体内与正在进行翻译的核糖体相关联,是高效翻译所必需的。Ctk1在Ser 238位点磷酸化小核糖体亚基的蛋白质Rps2。重要的是,Ctk1缺失的细胞以及rps2 - S238A突变细胞通过错义编码频率的增加表现出翻译延伸缺陷。Ctk1在翻译中的作用可能是保守的,因为Ctk1的哺乳动物同源物CDK9也与多核糖体相关联。由于Ctk1与将转录与mRNA输出相偶联的TREX(转录和mRNA输出)复合物相互作用,Ctk1/CDK9可能在转录过程中与正确加工的mRNA前体颗粒结合,并伴随mRNA前体颗粒到细胞质中的核糖体,在那里Ctk1增强mRNA的高效和准确翻译。