BioSysBio:abstracts/2007/Tao You

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A Quantitative Model for the GCN4 Translational Control in Saccharomyces cerevisiae

Author(s): Tao You 1,2, Alistair Brown 1, George Coghill 2
Affiliations: 1. Institute of Medical Sciences, University of Aberdeen, 2. Department of Computing Science, University of Aberdeen
Contact: t dot you at abdn dot ac dot uk
Keywords: translational regulation, kinetic model, parameter estimation

Abstract

Cells are capable of accommodating the environmental changes by reprogramming gene expression. In the yeast Saccharomyces cerevisiae, under the amino acid deprivation condition, the translational barrier primarily exerted on GCN4 mRNA is alleviated to enhance the production of Gcn4p, which subsequently induces the expression of nearly all genes involved in amino acid biosyntheses. Our Systems Biology project’s goal is to construct a dynamic mathematical model that accurately predicts the kinetic behaviour of the GCN Response in S. cerevisiae. Here, we report the mathematical formulations to describe the translational control exerted on the GCN4 mRNA. More importantly, the kinetic parameter estimation for this model indicates differential scanning rates of the 40S ribosomal subunit on the GCN4 mRNA 5’ leader sequence under the amino acid replete and starvation conditions. This discovery is speculated to be attributable to the change in relative helicase activities under the two conditions.

References

  1. Hinnebusch AG. Translational regulation of GCN4 and the general amino acid control of yeast. Annu Rev Microbiol. 2005;59:407-50. DOI:10.1146/annurev.micro.59.031805.133833 | PubMed ID:16153175 | HubMed [Hinnebusch-2005]
  2. Grant CM, Miller PF, and Hinnebusch AG. Requirements for intercistronic distance and level of eukaryotic initiation factor 2 activity in reinitiation on GCN4 mRNA vary with the downstream cistron. Mol Cell Biol. 1994 Apr;14(4):2616-28. PubMed ID:8139562 | HubMed [Grant-1994]
  3. D.T. Gillespie, Exact stochastic simulation of coupled chemical reactions, J Phys Chem 1977; 81(25) pp 2340 – 2361. [Gillespie-1977]
  4. Berthelot K, Muldoon M, Rajkowitsch L, Hughes J, and McCarthy JE. Dynamics and processivity of 40S ribosome scanning on mRNA in yeast. Mol Microbiol. 2004 Feb;51(4):987-1001. PubMed ID:14763975 | HubMed [Berthelot-2005]
  5. T. P. Runarsson and X. Yao, Stochastic Ranking for Constrained Evolutionary Optimization, IEEE Transactions on Evolutionary Computation 2000 Sep; 4(3):284-294. [Runarsson-2000]
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