Widespread selection for local RNA secondary structure in coding regions of bacterial genes
Widespread selection for local RNA secondary structure in coding regions of bacterial genes
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DOI：
10.1101/gr.1257503
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发表时间：
2003-09-01
期刊：
影响因子：
7
通讯作者：
Burge, CB
中科院分区：
文献类型：
--
作者：
Katz, L;Burge, CB
遗传密码的冗余决定了给定的蛋白质可以由大量不同的mRNA物种编码，这可能使mRNAs除了蛋白质编码功能外，还可以同时优化所需的RNA结构特征。为了确定天然mRNA是否存在与局部RNA二级结构相关的偏向，开发了一种新的随机化程序DicodonShuffle，它在保持与天然信息相同的编码蛋白质序列、相同的密码子使用和相同的二核苷酸组成的同时，将mRNA序列随机化。根据折叠自由能的测量，来自14个真细菌物种中的10个物种和一个真核生物--酵母酿酒酵母的基因显示出显著的偏向，有利于局部的RNA结构。一些重要的关联提示了mRNA结构的功能作用，包括在含有内含子的酵母基因的编码区比在无内含子的基因中有更强的二级结构偏向，以及在大肠杆菌中多顺反子信息的折叠潜力显著高于单顺反子信息。从大肠杆菌操纵子的5‘端到3’端，基因的潜在二级结构普遍增加，而同源伤寒沙门氏菌操纵子的二级结构潜力是保守的。这些结果从RNA结构在RNA加工、mRNA稳定性调节和翻译控制中的可能作用来解释。
Redundancy of the genetic code dictates that a given protein can be encoded by a large collection of distinct mRNA species, potentially allowing mRNAs to simultaneously optimize desirable RNA structural features in addition to their protein-coding function. To determine whether natural mRNAs exhibit biases related to local RNA secondary structure, a new randomization procedure was developed, DicodonShuffle, which randomizes mRNA sequences while preserving the same encoded protein sequence, the same codon usage, and the same dinucleotide composition as the native message. Genes from 10 of 14 eubacterial species studied and one eukaryote, the yeast Saccharomyces cerevisiae, exhibited statistically significant biases in favor of local RNA structure as measured by folding free energy. Several significant associations Suggest functional roles for mRNA structure, including stronger secondary structure bias in the coding regions of intron-containing yeast genes than in intronless genes, and significantly higher folding potential in polycistronic messages than in monocistronic messages in Escherichia coli. Potential secondary structure generally increased in genes from the 5' to the 3' end of E coli operons, and secondary structure potential was conserved in homologous Salmonella typhi operons. These results are interpreted in terms of possible roles of RNA structures in RNA processing, regulation of mRNA stability, and translational control.