An alternative adaptation strategy of the CCA-adding enzyme to accept non-canonical tRNA substrates in Ascaris suum.

Abstract

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 co-evolution 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 indicates that these enzymes evolved two distinct strategies to tolerate non-canonical 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.