A periodic pattern of mRNA secondary structure created by the genetic code.
A periodic pattern of mRNA secondary structure created by the genetic code.
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遗传密码产生的mRNA二级结构的周期性模式。
DOI：
10.1093/nar/gkl287
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发表时间：
2006
影响因子：
14.9
通讯作者：
Spiridonov, Nikolay A.
中科院分区：
文献类型：
--
作者：
Shabalina, Svetlana A.;Ogurtsov, Aleksey Y.;Spiridonov, Nikolay A.
单链mRNA分子通过互补的自相互作用形成二级结构。关于核苷酸序列、编码氨基酸序列与mRNA二级结构之间的关系，人们提出了几种假设。我们对人类和小鼠mRNA折叠进行了第一次转录组范围的计算机分析，发现核苷酸参与mRNA二级结构的明显周期性模式。我们发现这种模式是由遗传密码的结构造成的，二核苷酸的相对丰度对于维持mRNA的二级结构很重要。虽然同义密码子的使用有助于这种模式，但它是遗传密码结构的内在特征，即使在4倍简并位点没有同义密码子使用偏差的情况下也会表现出来。虽然所有密码子位点对维持mRNA二级结构都很重要，但密码子的简并可以调节mRNA二级结构的稳定性和周期性。我们证明了第三个简并密码子位点对mRNA的稳定性贡献最大。这些结果令人信服地支持了遗传密码中的冗余允许转录本满足蛋白质结构和RNA结构要求的假设。我们的数据表明，选择可能在同义密码子上运行，以维持更稳定和有序的mRNA二级结构，这可能对转录稳定性和翻译很重要。我们还证明了mRNA的功能域[5 ' -非翻译区（5 ' -UTR）， CDS和3 ' -UTR]优先折叠到自己上，而开始密码子和停止密码子区域具有松弛的二级结构，这可能有助于翻译的起始和终止。
Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleotide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both protein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA secondary structure, which is likely to be important for transcript stability and translation. We also demonstrate that functional domains of the mRNA [5′-untranslated region (5′-UTR), CDS and 3′-UTR] preferentially fold onto themselves, while the start codon and stop codon regions are characterized by relaxed secondary structures, which may facilitate initiation and termination of translation.
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