Abstract
Translation is a central biological process by which proteins are synthesized from genetic information contained within mRNAs. Here, we investigate the kinetics of translation at the molecular level by a stochastic simulation model. The model explicitly includes RNA sequences, ribosome dynamics, the tRNA pool and biochemical reactions involved in the translation elongation. The results show that the translation efficiency is mainly limited by the available ribosome number, translation initiation and the translation elongation time. The elongation time is a log-normal distribution, with the mean and variance determined by the codon saturation and the process of aa-tRNA selection at each codon binding site. Moreover, our simulations show that the translation accuracy exponentially decreases with the sequence length. These results suggest that aa-tRNA competition is crucial for both translation elongation, translation efficiency and the accuracy, which in turn determined the effective protein production rate of correct proteins. Our results improve the dynamical equation of protein production with a delay differential equation that is dependent on sequence information through both the effective production rate and the distribution of elongation time.
Highlights
Translation is a central biological process by which genetic information contained within mRNAs is interpreted to generate proteins
Our results show that the translation efficiency is mainly limited by the number of the available ribosomes, translation initiation and the elongation time of translation, and the elongation time is log-normal distribution with mean and variance of the logarithm of the elongation time dependent on the sequence through aminoacylated tRNA (aa-tRNA) usages
Translation of a protein begins from the initiation stage by which the start codon (AUG site) of the mRNA sequence is occupied by a ribosome, and the peptide between the first two amino acids are formed, with corresponding aa-tRNAs binding to the E and P sites of the ribosome, respectively
Summary
Translation is a central biological process by which genetic information contained within mRNAs is interpreted to generate proteins. Computational models have been developed to investigate details of the translation kinetics and to explore the main factors that affect the translation efficiency, such as codon bias, tRNA and ribosome competition, ribosome queuing, codon order [2, 3, 6, 14, 19, 20, 21] In these models, status of all ribosomes and tRNAs along a mRNA are tracked in continuous time. A study based on a computation model with detailed tRNA pool composition shows that the competition between near-cognate and cognate tRNAs is a key factor that determines the translation rate [6]. Much details of how translation is controlled by mRNA sequences and cellular environment remain exclusive Both the number of available free ribosomes and the codon orders are important for translation efficiency, how various factors combine to determine the translation efficiency is not clearly formulated. These results provide more detailed understanding of the translation processes, and can improve the mathematical modeling of protein production in gene regulation network dynamics
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