Katz Luba, Burge Christopher B
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Genome Res. 2003 Sep;13(9):2042-51. doi: 10.1101/gr.1257503.
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.
遗传密码的冗余性表明，一种特定的蛋白质可以由大量不同的mRNA种类编码，这可能使mRNA除了其蛋白质编码功能外，还能同时优化理想的RNA结构特征。为了确定天然mRNA是否表现出与局部RNA二级结构相关的偏好，人们开发了一种新的随机化程序——双密码子洗牌（DicodonShuffle），该程序在保持与天然信息相同的编码蛋白质序列、相同的密码子使用情况和相同的二核苷酸组成的同时，对mRNA序列进行随机化处理。在所研究的14种真细菌中的10种以及一种真核生物——酿酒酵母（Saccharomyces cerevisiae）的基因中，通过折叠自由能测量发现，它们在局部RNA结构方面表现出统计学上显著的偏好。一些显著的关联表明了mRNA结构的功能作用，包括含内含子的酵母基因编码区的二级结构偏好性比无内含子基因更强，以及在大肠杆菌中，多顺反子信息的折叠潜力明显高于单顺反子信息。在大肠杆菌操纵子中，从5'端到3'端的基因，其潜在二级结构通常会增加，并且在同源的伤寒沙门氏菌操纵子中，二级结构潜力是保守的。这些结果从RNA结构在RNA加工、mRNA稳定性调控和翻译控制中的可能作用方面进行了解释。
