Intramural Research Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
RNA. 2014 Jul;20(7):977-84. doi: 10.1261/rna.044115.113.
Whole-genome and functional analyses suggest a wealth of secondary or auxiliary genetic information (AGI) within the redundancy component of the genetic code. Although there are multiple aspects of biased codon use, we focus on two types of auxiliary information: codon-specific translational pauses that can be used by particular proteins toward their unique folding and biased codon patterns shared by groups of functionally related mRNAs with coordinate regulation. AGI is important to genetics in general and to human disease; here, we consider influences of its three major components, biased codon use itself, variations in the tRNAome, and anticodon modifications that distinguish synonymous decoding. AGI is plastic and can be used by different species to different extents, with tissue-specificity and in stress responses. Because AGI is species-specific, it is important to consider codon-sensitive experiments when using heterologous systems; for this we focus on the tRNA anticodon loop modification enzyme, CDKAL1, and its link to type 2 diabetes. Newly uncovered tRNAome variability among humans suggests roles in penetrance and as a genetic modifier and disease modifier. Development of experimental and bioinformatics methods are needed to uncover additional means of auxiliary genetic information.
全基因组和功能分析表明，遗传密码冗余成分中存在大量的二级或辅助遗传信息（AGI）。尽管偏倚密码子使用有多个方面，但我们主要关注两种辅助信息：特定蛋白质用于其独特折叠的密码子特异性翻译暂停，以及具有协调调控的功能相关 mRNA 组共享的偏倚密码子模式。AGI 对遗传学一般和人类疾病都很重要；在这里，我们考虑了它的三个主要组成部分的影响，即偏倚密码子使用本身、tRNAome 的变化以及区分同义解码的反密码子修饰。AGI 具有可塑性，可以被不同物种在不同程度上使用，具有组织特异性和应激反应性。由于 AGI 是物种特异性的，因此在使用异源系统时，考虑密码子敏感实验非常重要；为此，我们重点关注 tRNA 反密码子环修饰酶 CDKAL1 及其与 2 型糖尿病的联系。人类中发现的新的 tRNAome 变异性表明其在穿透性和作为遗传修饰因子和疾病修饰因子方面的作用。需要开发实验和生物信息学方法来揭示辅助遗传信息的其他手段。
