Thalhofer Valerie, Doktor Claudius, Philipp Lena, Betat Heike, Mörl Mario
Institute for Biochemistry, Leipzig University, Leipzig, Germany.
Institute for Biochemistry, Leipzig University, Leipzig, Germany.
J Biol Chem. 2025 Apr;301(4):108414. doi: 10.1016/j.jbc.2025.108414. Epub 2025 Mar 17.
Playing a central role in translation, tRNAs act as an essential adapter linking the correct amino acid to the corresponding mRNA codon in translation. Due to this function, all tRNAs exhibit a typical secondary and tertiary structure to be recognized by the tRNA maturation enzymes as well as many components of the translation machinery. Yet, there is growing evidence for structurally deviating tRNAs in metazoan mitochondria, requiring a coevolution and adaptation of these enzymes to the unusual structures of their substrates. Here, it is shown that the CCA-adding enzyme of Ascaris suum carries such a specific adaptation in form of a C-terminal extension. The corresponding enzymes of other nematodes also carry such extensions, and many of them have an additional adaptation in a small region of their N-terminal catalytic core. Thus, the presented data indicate that these enzymes evolved two distinct strategies to tolerate noncanonical tRNAs as substrates for CCA incorporation. The identified C-terminal extension represents a surprising case of convergent evolution in tRNA substrate adaptation, as the nematode mitochondrial translation factor EF-Tu1 carries a similar extension that is essential for efficient binding to such structurally deviating tRNAs.
转运RNA（tRNA）在翻译过程中发挥核心作用，作为一种重要的衔接分子，在翻译过程中将正确的氨基酸连接到相应的信使核糖核酸（mRNA）密码子上。由于这一功能，所有tRNA都呈现出典型的二级和三级结构，以便被tRNA成熟酶以及翻译机制的许多组分识别。然而，越来越多的证据表明后生动物线粒体中存在结构异常的tRNA，这就需要这些酶与其底物的异常结构共同进化并适应。本文表明，猪蛔虫的CCA添加酶以C端延伸的形式具有这样一种特异性适应。其他线虫的相应酶也有这样的延伸，并且其中许多在其N端催化核心的一个小区域还有额外的适应性变化。因此，所呈现的数据表明，这些酶进化出了两种不同的策略来耐受非规范tRNA作为CCA掺入的底物。所鉴定出的C端延伸代表了tRNA底物适应中趋同进化的一个惊人例子，因为线虫线粒体翻译因子EF-Tu1带有类似的延伸，这对于有效结合此类结构异常的tRNA至关重要。
