Codon Translation Rates Are Uniform?!

" Differential codon usage has been hypothesized as a regulator of protein synthesis rates, with rare codons with lower tRNA concentrations thought to slow translation. Ribosome Profiling experiments provide a snapshot of the location of all of the ribosomes as they translate messenger RNA. By analyzing codon dwell times, we investigate the dependence on tRNA concentration. We find only a very slight correlation, indicating that the peptide transfer or translocation steps, and not tRNA accommodation, is rate limiting in translation. The statistical distribution of Ribosome Profiling counts is very wide and skewed. Genes have a few codons where ribosome occupancy is many times the mean, and many locations that are significantly below the mean. We find that a Poisson Log-Normal (PLN) is an excellent descriptor of the distribution of counts in genes. Furthermore, the PLN standard deviation parameter is nearly universal for genes with mean counts ranging across many orders of magnitude. All codons exhibit a wide range of translation speeds, from fast and slow. The cause of the speed variations is unknown, but our analysis shows speeds in replicates are correlated. Ribosomes normally translate messages with a three base (codon) periodicity. Occasion- ally the ribosome slips, and the frame-shifted message is translated. Often these shifts lead quickly to stop codons, but we designed synonymous sequences without out-of-frame inter- nal stops to study protein production ending in all three reading frames. Our experiments include a gene with a known −1 frameshift, one with a known +1 frameshift, and another to test whether frameshifting is responsible for attenuated protein production. Preliminary experimental results are reported."

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