Widespread Cotranslational Formation of Protein Complexes
Widespread Cotranslational Formation of Protein Complexes
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DOI：
10.1371/journal.pgen.1002398
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发表时间：
2011-12-01
期刊：
影响因子：
4.5
通讯作者：
Mata, Juan
中科院分区：
文献类型：
--
作者：
Duncan, Caia D. S.;Mata, Juan
大多数细胞过程是由多蛋白复合物进行的。然而，人们对这些复合物是如何组装的知之甚少。特别是，不知道它们是否是在复合物的一个或多个成员被翻译时形成的（共翻译组装）。我们采用基因组方法来解决这个问题，通过系统地识别与特定蛋白质相关的mRNA。在来自粟酒裂殖酵母的31种不含RNA结合结构域的蛋白质样品中，我们发现类似于38%的蛋白质与编码相互作用蛋白质的mRNA共纯化。例如，细胞周期蛋白依赖性激酶Cdc 2 p与rum 1和cdc 18 mRNA相关，它们分别编码Cdc 2 p激酶活性的抑制剂和DNA复制的重要调节因子。这两种蛋白质与Cdc 2 p相互作用，是关键的细胞周期调节因子。我们得到了类似的结果与不同的结构和细胞功能的蛋白质（驱动蛋白，蛋白激酶，转录因子，蛋白酶体成分等）。我们发现，copurification的诱饵蛋白和特定的mRNA依赖于存在的蛋白质编码的相互作用的mRNA和多核糖体的完整性。这些结果表明，这些观察到的协会反映了诱饵和新生蛋白质之间的相互作用的mRNA编码的共翻译相互作用。因此，我们发现蛋白质-蛋白质相互作用的共翻译形成是一种普遍现象。
Most cellular processes are conducted by multi-protein complexes. However, little is known about how these complexes are assembled. In particular, it is not known if they are formed while one or more members of the complexes are being translated (cotranslational assembly). We took a genomic approach to address this question, by systematically identifying mRNAs associated with specific proteins. In a sample of 31 proteins from Schizosaccharomyces pombe that did not contain RNA-binding domains, we found that similar to 38% copurify with mRNAs that encode interacting proteins. For example, the cyclin-dependent kinase Cdc2p associates with the rum1 and cdc18 mRNAs, which encode, respectively, an inhibitor of Cdc2p kinase activity and an essential regulator of DNA replication. Both proteins interact with Cdc2p and are key cell cycle regulators. We obtained analogous results with proteins with different structures and cellular functions (kinesins, protein kinases, transcription factors, proteasome components, etc.). We showed that copurification of a bait protein and of specific mRNAs was dependent on the presence of the proteins encoded by the interacting mRNAs and on polysomal integrity. These results indicate that these observed associations reflect the cotranslational interaction between the bait and the nascent proteins encoded by the interacting mRNAs. Therefore, we show that the cotranslational formation of protein-protein interactions is a widespread phenomenon.