Department of Biology, University of Oslo, Center for Ecological and Evolutionary Synthesis, Blindern, 3016 Oslo, Norway.
Biol Direct. 2010 Jun 16;5:39. doi: 10.1186/1745-6150-5-39.
The hypothesis that both mitochondrial (mt) complementary DNA strands of tRNA genes code for tRNAs (sense-antisense coding) is explored. This could explain why mt tRNA mutations are 6.5 times more frequently pathogenic than in other mt sequences. Antisense tRNA expression is plausible because tRNA punctuation signals mt sense RNA maturation: both sense and antisense tRNAs form secondary structures potentially signalling processing. Sense RNA maturation processes by default 11 antisense tRNAs neighbouring sense genes. If antisense tRNAs are expressed, processed antisense tRNAs should have adapted more for translational activity than unprocessed ones. Four tRNA properties are examined: antisense tRNA 5' and 3' end processing by sense RNA maturation and its accuracy, cloverleaf stability and misacylation potential.
Processed antisense tRNAs align better with standard tRNA sequences with the same cognate than unprocessed antisense tRNAs, suggesting less misacylations. Misacylation increases with cloverleaf fragility and processing inaccuracy. Cloverleaf fragility, misacylation and processing accuracy of antisense tRNAs decrease with genome-wide usage of their predicted cognate amino acid.
These properties correlate as if they adaptively coevolved for translational activity by some antisense tRNAs, and to avoid such activity by other antisense tRNAs. Analyses also suggest previously unsuspected particularities of aminoacylation specificity in mt tRNAs: combinations of competition between tRNAs on tRNA synthetases with competition between tRNA synthetases on tRNAs determine specificities of tRNA amino acylations. The latter analyses show that alignment methods used to detect tRNA cognates yield relatively robust results, even when they apparently fail to detect the tRNA's cognate amino acid and indicate high misacylation potential.
本文探索了线粒体（mt）tRNA 基因的两条互补 DNA 链都编码 tRNA（反义编码）的假说。这可以解释为什么 mt tRNA 突变的致病性比其他 mt 序列高 6.5 倍。反义 tRNA 的表达是合理的，因为 tRNA 标点信号 mt sense RNA 的成熟： sense 和 antisense tRNA 都形成二级结构，可能表明加工过程。 sense RNA 成熟过程默认处理 11 个邻近 sense 基因的反义 tRNA。如果反义 tRNA 表达，那么经过加工的反义 tRNA 应该比未加工的更适合翻译活性。本文检查了四个 tRNA 特性： sense RNA 成熟过程中反义 tRNA 的 5'和 3'端加工及其准确性、三叶草叶结构的稳定性和错酰化潜力。
经过加工的反义 tRNA 与具有相同对应物的标准 tRNA 序列更匹配，表明错酰化程度较低。错酰化程度随着三叶草叶结构的脆弱性和加工准确性的增加而增加。反义 tRNA 的三叶草叶结构的脆弱性、错酰化和加工准确性随着其预测的对应氨基酸在全基因组中的使用而降低。
这些特性的相关性表明，某些反义 tRNA 通过某种方式适应了翻译活性的协同进化，而其他反义 tRNA 则避免了这种活性。分析还表明，mt tRNA 的氨酰化特异性存在以前未被怀疑的特殊性： tRNA 合成酶上 tRNA 之间的竞争与 tRNA 合成酶上 tRNA 之间的竞争相结合，决定了 tRNA 氨酰化的特异性。后一种分析表明，即使它们显然无法检测到 tRNA 的对应氨基酸，并且表明存在高错酰化潜力，用于检测 tRNA 对应物的对齐方法也能产生相对稳健的结果。
