Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria.
Nucleic Acids Res. 2012 Oct;40(18):8874-82. doi: 10.1093/nar/gks679. Epub 2012 Jul 25.
A potential connection between physico-chemical properties of mRNAs and cognate proteins, with implications concerning both the origin of the genetic code and mRNA-protein interactions, is unexplored. We compare pyrimidine content of naturally occurring mRNA coding sequences with the propensity of cognate protein sequences to interact with pyrimidines. The latter is captured by polar requirement, a measure of solubility of amino acids in aqueous solutions of pyridines, heterocycles closely related to pyrimidines. We find that the higher the pyrimidine content of an mRNA, the stronger the average propensity of its cognate protein's amino acids to interact with pyridines. Moreover, window-averaged pyrimidine profiles of individual mRNAs strongly mirror polar-requirement profiles of cognate protein sequences. For example, 4953 human proteins exhibit a correlation between the two with |R| > 0.8. In other words, pyrimidine-rich mRNA regions quantitatively correspond to regions in cognate proteins containing residues soluble in pyrimidine mimetics and vice versa. Finally, by studying randomized genetic code variants we show that the universal genetic code is highly optimized to preserve these correlations. Overall, our findings redefine the stereo-chemical hypothesis concerning code's origin and provide evidence of direct complementary interactions between mRNAs and cognate proteins before development of ribosomal decoding, but also presently, especially if both are unstructured.
mRNA 的理化性质与其对应蛋白之间可能存在联系，这对遗传密码的起源和 mRNA-蛋白相互作用都有影响，但这一联系尚未被探索。我们比较了天然存在的 mRNA 编码序列中的嘧啶含量与其对应蛋白序列与嘧啶相互作用的倾向。后者由极性要求来衡量，极性要求是指氨基酸在吡啶、嘧啶等与嘧啶密切相关的杂环水溶液中的溶解度。我们发现，mRNA 的嘧啶含量越高，其对应蛋白的氨基酸与嘧啶相互作用的平均倾向就越强。此外，单个 mRNA 的窗口平均嘧啶分布强烈反映了对应蛋白序列的极性要求分布。例如，4953 个人类蛋白质在这两者之间具有 |R| > 0.8 的相关性。换句话说，富含嘧啶的 mRNA 区域在数量上与含有在嘧啶类似物中可溶残基的对应蛋白区域相对应，反之亦然。最后，通过研究随机化的遗传密码变体，我们表明，通用遗传密码高度优化以保留这些相关性。总的来说，我们的发现重新定义了关于密码起源的立体化学假说，并提供了核糖体解码前 mRNA 和对应蛋白之间直接互补相互作用的证据，但目前也存在这种相互作用，特别是在两者都没有结构的情况下。
