Ribosome-associated quality control of aberrant protein production during amino acid limitation

Amino acids can become limiting for protein synthesis through depletion of charged tRNAs, leading to ribosome stalling and disruption of translation elongation at specific codons. To assess whether this is a mechanism by which amino acid availability can directly influence gene expression, we designed a reporter library to measure translation disruption across all sense codons in the context of amino acid limitations in human cancer/transformed cell lines. Charged tRNA sequencing was used during limitation for several amino acids to validate reporter survey results and uncover the mechanisms behind codon-specific translation disruption. Proteomics with paired RNA sequencing was used to define consequences for endogenous protein synthesis. These sequencing data sets are submitted for public access.