Post-Translational Modifications Guard Yeast from Misaspartylation

Yeast aspartyl-tRNA synthetase (AspRS) is downregulated at the post-transcriptional level. This complex retro-inhibition mechanism causes the cell to equilibrate cellular concentrations of tRNA(Asp), AspRS, and its encoding mRNA. This strategy hinders AspRS accumulation to keep misacylation of heterologous tRNAs under control. Here, the AspRS concentration was increased artificially in vivo but did not generate tRNA(Asn) and/or tRNA(Glu) misaspartylation or the logical consecutive post-translational stress. This work allowed the detection of-an additional subtle cellular lock capable of blocking AspRS toxicity. This study revealed the presence of post-translational modifications in the N-terminal extension of AspRS. We hypothesize that by neutralizing the lysine-rich motif contained in this domain, the cell mobilizes an additional strategy that considerably reduces the probability of the enzyme binding and aspartylating noncognate tRNAs and thus harming its own translation.