Deciphering translation - a genome-wide analysis of translation in Escherichia coli
Protein synthesis is one of the central elements in every living cell. For this process, mRNAs coding for genes are simultaneously competing for the same translation machinery (ribosomes and amino acids). But the ultimate determinants of cellular functions are the proteins, a good understanding of this process is therefore of crucial importance. For this purpose, we developed a genome-wide, mechanistic, mathematical model of translation, taking into account individual codon kinetics. It is used to quantify the rate limiting steps of translation and gain insight into the mechanism of regulation of expression between different proteins. We observe for each gene in a first low-occupancy phase a nearly linear increase in protein synthesis rate with amount of bound ribosomes to the mRNA, followed by a plateau of maximum synthesis rate. A further increase in the ribosomal coverage of the mRNA leads to a decrease in protein production rate, and might act as sinks for system resources like ribosomes. Native E. coli gene sequences are also compared to randomly obtained synonymous sequences, coding the same protein, and it is found some genes of higher significance for the cell have been better optimized for protein synthesis rate than other.
Record created on 2014-11-04, modified on 2016-08-09