Evolutionarily-Encoded Translation Kinetics Coordinate Co-Translational Ssb Chaperone Binding In Yeast

Chaperones can bind to the ribosomes and nascent polypeptides co-translationally to assist protein folding. It was not known previously whether there is any interplay between chaperone binding and translation kinetics. To study this effect, we utilize the high-throughput transcriptome-wide quantitative data for translation kinetics and chaperone binding from ribosome profiling and selective ribosome profiling methods respectively. In vivo selective ribosome profiling has shown that yeast Hsp70 chaperone Ssb associates broadly with a major fraction of nascent proteins. Using the ribosome footprint densities as a measure of local translation rate, we find that mRNA segments within the ribosome are translated faster during periods of Ssb binding to the nascent polypeptides compared to when Ssb is not bound. The acceleration of translation is maintained even when Ssb is knocked out thus implying an inherent encoding of faster translation within the mRNA sequence. Testing for mRNA features that can slow translation, we find that mRNA segments translated by Ssb-engaged ribosomes are enriched for fast-translated codons (having higher cognate tRNA concentrations), are depleted for slowly translated codons, and contain fewer proline codons. In addition, mRNA segments located 1-15 nucleotides downstream of Ssb-bound ribosomes have reduced mRNA secondary structure. Finally, nascent chain segments located in the ribosome tunnel of Ssb-bound ribosomes have average numbers of positively charged residues but are enriched in negatively charged residues. Taken together, these evolutionarily-encoded mRNA and nascent chain features cause faster translation during Ssb binding. This finding is significant as any alteration of translation kinetics due to synonymous mutations can potentially disrupt efficient binding of Ssb leading to possible misfolding of the protein without any change in its sequence.