Optimized TRNA Allocation Partially Explains Efficient Translation In Saccharomyces Cerevisiae

Deciphering the rule of tRNA allocation and its effect on elongation rate is a central subject of the researches on translation regulation, as tRNA significantly affects translation efficiency and accuracy. In this study, we analyzed the codon frequency at the A sites of translating ribosomes based on the ribosome profiling data in yeast. We found a significant tendency to avoid translating identical codons at the same time, especially for the codons recognized by low concentration tRNAs. Moreover, the tendency is significant in highly translated mRNAs, while not obvious in the mRNAs with low ribosome density. To explain the results, we subsequently simulated the translation processes of highly translated mRNAs using a computational model, where all mRNAs are translated at the same time and tRNA competition exists among translating ribosomes. Strikingly, we found a significant decrease in the elongation rate when translating random sequences compared with that in the translation of native sequences. Further evidence showed that the reduced elongation rate is due to the decrease in the number of the effective tRNAs that can recognize the codons that are being translated. Based on these results, we concluded that there is an optimal tRNA allocation during translation, which can reduce the probability of tRNA competition among translating ribosomes, decreasing the time waiting for tRNAs and thus leading to an efficient translation.