Sequence-specific targeting of Caenorhabditis elegans C-Ala to the D-loop of tRNA Ala .

Alanyl-tRNA synthetase retains a conserved prototype structure throughout its biology. Nevertheless, its C-terminal domain (C-Ala) is highly diverged and has been shown to play a role in either tRNA or DNA binding. Interestingly, we discovered that Caenorhabditis elegans cytoplasmic C-Ala (Ce-C-Ala _c ) robustly binds both ligands. How Ce-C-Ala _c targets its cognate tRNA and whether a similar feature is conserved in its mitochondrial counterpart remain elusive. We show that the N- and C-terminal subdomains of Ce-C-Ala _c are responsible for DNA and tRNA binding, respectively. Ce-C-Ala _c specifically recognized the conserved invariant base G ¹⁸ in the D-loop of tRNA ^Ala through a highly conserved lysine residue, K934. Despite bearing little resemblance to other C-Ala domains, C. elegans mitochondrial C-Ala robustly bound both tRNA ^Ala and DNA and maintained targeting specificity for the D-loop of its cognate tRNA. This study uncovers the underlying mechanism of how C. elegans C-Ala specifically targets the D-loop of tRNA ^Ala .
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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