Specificity of RNA Folding and Its Association with Evolutionarily Adaptive mRNA Secondary Structures
Specificity of RNA Folding and Its Association with Evolutionarily Adaptive mRNA Secondary Structures
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RNA 折叠的特异性及其与进化适应性 mRNA 二级结构的关联
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发表时间：
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影响因子：
9.5
通讯作者：
杨建荣
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作者：
余功旺;朱寒冰;陈小舒;杨建荣
二级结构是非编码RNA和信使RNA的基本特征。然而，我们对mRNA的二级结构，特别是编码区的二级结构的理解仍然难以捉摸，可能是由于翻译和缺乏维持共有结构的RNA结合蛋白，例如那些与非编码RNA结合的蛋白。事实上，最近发现mRNA具有多种替代结构，其总体功能意义尚未得到验证。因此，我们通过估计折叠特异性，即，一段RNA重折叠后折叠回同一个伴侣的可能性。我们发现mRNA的折叠特异性低于非编码RNA，并表现出适度的进化保守性。值得注意的是，我们发现特异性折叠而不是选择性折叠可能是进化适应性的，因为特异性折叠经常与功能重要的基因或基因内的位点相关。结合核糖体密度的额外分析表明，调节核糖体运动的能力是特异性折叠提供的一个潜在功能优势。我们的研究结果揭示了一个新的方面的RNA结构具有重要的功能和进化意义，并指出了一个潜在的方法区分mRNA二级结构保持自然选择的分子噪音。
The secondary structure is a fundamental feature of both noncoding and messenger RNAs. However, our understanding of the secondary structure of mRNA, especially that of the coding regions, remains elusive, likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure, such as those that bind to noncoding RNA. Indeed, mRNA has recently been found to adopt diverse alternative structures, the overall functional significance of which remains untested. We hereby approached this problem by estimating the folding specificity, i.e., the probability that a fragment of RNA folds back to the same partner once refolded. We showed that the folding specificity of mRNA is lower than that of noncoding RNA and exhibits moderate evolutionary conservation. Notably, we found that specific rather than alternative folding is likely evolutionarily adaptive, since specific folding is frequently associated with functionally important genes or sites within a gene. Additional analysis in combination with ribosome density suggests the ability to modulate ribosome movement as one potential functional advantage provided by specific folding. Our findings revealed a novel facet of the RNA structurome with important functional and evolutionary implications and indicated a potential method for distinguishing the mRNA secondary structures maintained by natural selection from molecular noise.