Sequence signatures of direct complementarity between mRNAs and cognate proteins on multiple levels
Sequence signatures of direct complementarity between mRNAs and cognate proteins on multiple levels
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DOI：
10.1093/nar/gks679
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发表时间：
2012-10-01
影响因子：
14.9
通讯作者：
Zagrovic, Bojan
中科院分区：
文献类型：
--
作者：
Hlevnjak, Mario;Polyansky, Anton A.;Zagrovic, Bojan
MRNAs和同源蛋白的物理化学性质之间的潜在联系，与遗传密码的起源和mRNAs-蛋白质的相互作用有关，尚未被探索。我们比较了自然产生的信使核糖核酸编码序列的嘧啶含量与同源蛋白序列与嘧啶相互作用的倾向。后者被极性需求捕获，这是一种衡量氨基酸在吡啶水溶液中的溶解度的指标，吡啶是与嘧啶密切相关的杂环。我们发现，mRNA中的嘧啶含量越高，其同源蛋白的氨基酸与吡啶相互作用的平均倾向就越强。此外，窗口平均的单个mRNAs的嘧啶分布强烈地反映了同源蛋白质序列的极性需求分布。例如，4953种人类蛋白质与|R|>；0.8之间存在相关性。换句话说，富含嘧啶的信使核糖核酸区域在数量上对应于同源蛋白中含有可溶于嘧啶模拟物的残基的区域，反之亦然。最后，通过对随机遗传密码变体的研究，我们发现通用遗传密码高度优化以保持这些相关性。总体而言，我们的发现重新定义了关于CODE起源的立体化学假说，并提供了在核糖体解码发展之前以及现在，特别是如果两者都是非结构化的情况下，mRNAs和同源蛋白之间直接互补相互作用的证据。
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.