Ribosome traffic on mRNAs maps to gene ontology : genome-wide quantification of translation initiation rates and polysome size regulation

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Identification of the mRNA targets of tRNA-specific regulation using genome-wide simulation of translation

FUNDING Biotechnology and Biological Sciences Research Council (BBSRC) [BB/I020926/1 to I.S.]; BBSRC PhD studentship award [C103817D to I.S. and M.C.R.]; Scottish Universities Life Science Alliance PhD studentship award (to M.C.R. and I.S.]. Funding for open access charge: BBSRC. Conflict of interest statement. None declared.Peer reviewedPublisher PD

ExpressInHost : A codon tuning tool for the expression of recombinant proteins in host microorganisms

Funding Information This work was performed as part of the Innovate UK project “Predictive optimisation of biocatalyst production for high-value chemical manufacturing” (Project Number TP101439). The current position of A.R. is funded by the German federal and state programme Professorinnenprogramms III for female scientists.Peer reviewedPublisher PD

ExpressInHost: A codon tuning tool for the expression of recombinant proteins in host microorganisms

ExpressInHost (https://gitlab.com/a.raguin/expressinhost) is a GTK/C++ based user friendly graphical interface that allows tuning the codon sequence of an mRNA for recombinant protein expression in a host microorganism. Heterologous gene expression is widely implemented in biotechnology companies and academic research laboratories. However, expression of recombinant proteins can be challenging. On the one hand, maximising translation speed is important, especially in scalable production processes relevant to biotechnology companies, but on the other hand, solubility problems often arise as a consequence, since translation "pauses" might be key to allow the nascent polypeptide chain to fold appropriately. To address this challenge, we have developed a software that offers three distinct modes to tune codon sequences using the genetic code redundancy. The tuning strategies implemented take into account the specific tRNA resources of the host and that of the native organism. They balance rapid translation and native speed mimicking to allow proper protein folding, thereby avoiding protein solubility problems

Analysing GCN4 Translational Control in Yeast by Stochastic Chemical Kinetics Modelling and Simulation

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tRNA properties help shape codon pair preferences in open reading frames

Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three distinct and marked effects were revealed once codon and dipeptide biases had been subtracted. First, in the majority of genomes, codon pair preference is primarily determined by a tetranucleotide combination of the third nucleotide of the P-site codon, and all 3 nt of the A-site codon. Second, pairs of rare codons are generally under-used in eukaryotes, but over-used in prokaryotes. Third, the analysis revealed a highly significant effect of tRNA-mediated selection on codon pairing in unicellular eukaryotes, Bacillus subtilis, and the gamma proteobacteria. This was evident because in these organisms, synonymous codons decoded in the A-site by the same tRNA exhibit significantly similar P-site pairing preferences. Codon pair preference is thus influenced by the identity of A-site tRNAs, in combination with the P-site codon third nucleotide. Multivariate analysis identified conserved nucleotide positions within A-site tRNA sequences that modulate codon pair preferences. Structural features that regulate tRNA geometry within the ribosome may govern genomic codon pair patterns, driving enhanced translational fidelity and/or rate

Definition Of The Minimal Contents For The Molecular Simulation Of The Yeast Cytoplasm

Funding VK gratefully acknowledges the receipt of a scholarship under the Aberdeen-Curtin Alliance collaborative Ph.D. program. Acknowledgments We thank Prof. Grant Brown (University of Toronto) for making the yeast proteomics datasets available to us.Peer reviewedPublisher PD

What determines sub-diffusive behavior in crowded protein solutions?

This work used the ARCHER UK National Supercomputing Service (http://www.archer.ac.uk), access to which was provided by the UK High-End Computing Consortium for Biomolecular Simulation, HECBioSim (https://www.hecbiosim.ac.uk/), supported by EPSRC (grant no. EP/R029407/1). Analysis and visualization of the simulation data were conducted at the Pawsey Supercomputing Centre, therefore this work was supported by resources provided by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia, as well as resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government. V.K. gratefully acknowledges the receipt of a scholarship under the Aberdeen-Curtin Alliance collaborative PhD program.Peer reviewedPostprin

Novel mRNA-specific effects of ribosome drop-off on translation rate and polysome profile

IS and MCR were supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (http://www.bbsrc.ac.uk) BB/N017161/1. IS was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (http://www.bbsrc.ac.uk) BB/I020926/1. PB and MCR were supported by the Scottish Universities Life Sciences Alliance (SULSA) (http://www.sulsa.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD