Chu, Dominique and Barnes, David J. and von der Haar, Tobias (2011) The role of tRNA and ribosome competition in coupling the expression of different mRNAs in Saccharomyces cerevisiae. Nucleic Acids Research, 39 (15). pp. 6705-6714. ISSN 0305-1048. (Full text available)
Available under License Creative Commons Attribution Non-commercial.
Protein synthesis translates information from messenger RNAs into functional proteomes. Because of the finite nature of the resources required by the translational machinery, both the overall protein synthesis activity of a cell and activity on individual mRNAs are controlled by the allocation of limiting resources. Upon introduction of heterologous sequences into an organism—for example for the purposes of bioprocessing or synthetic biology—limiting resources may also become overstretched, thus negatively affecting both endogenous and heterologous gene expression. In this study, we present a mean-field model of translation in Saccharomyces cerevisiae for the investigation of two particular translational resources, namely ribosomes and aminoacylated tRNAs. We firstly use comparisons of experiments with heterologous sequences and simulations of the same conditions to calibrate our model, and then analyse the behaviour of the translational system in yeast upon introduction of different types of heterologous sequences. Our main findings are that: competition for ribosomes, rather than tRNAs, limits global translation in this organism; that tRNA aminoacylation levels exert, at most, weak control over translational activity; and that decoding speeds and codon adaptation exert strong control over local (mRNA specific) translation rates.
|Uncontrolled keywords:||determinacy analysis, Craig interpolants|
|Subjects:||Q Science > QP Physiology (Living systems)
Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QR Microbiology
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences
Faculties > Science Technology and Medical Studies > School of Computing
Faculties > Science Technology and Medical Studies > School of Computing > Computational Intelligence Group
|Depositing User:||David Barnes|
|Date Deposited:||01 Sep 2011 11:39|
|Last Modified:||20 Nov 2014 14:45|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/28074 (The current URI for this page, for reference purposes)|