Firczuk2013 - Eukaryotic mRNA translation machinery

  public model
Model Identifier
BIOMD0000000457
Short description
Firczuk2013 - Eukaryotic mRNA translation machinery

This is a model of Saccharomyces cerevisiae mRNA translation which includes the initiation, elongation and termination phases. The model is for 20 condon mRNAs. The building of a multi-factor complex in initiation and also the different processes in elongation and termination are modelled in detail. The model takes into account that ribosomes cover more than one codon of mRNA so that the movement of ribosomes are effectively blocked by other ribosomes several codons downstream. It is assumed that 15 codons are occupied by each ribosome. This blocking effect is considered in reaction R18 in initiation and also reaction R26, the reaction where translocation of ribosomes takes place in elongation. The kinetic functions of these two reactions are based on MacDonald et al. 1968 and Heinrich & Rapaport 1980. All other kinetic functions follow mass-action kinetics. The concentrations of transfer RNA species (Met-tRNA, aa-tRNA and tRNA in the model) are kept constant, while the other species' concentrations can change in the course of the simulation. The model describes the translation of a short mRNA with 20 codons. Therefore, all reactions in the elongation cycle (R22, R23, R25, R26, R28 and R29) and the corresponding species are replicated accordingly to model the species with ribosomes bound at different positions. In summary, the model contains 165 different species and 141 reactions.

The value of the 56 rate constant parameters were estimated by fitting the model against a series of experimental data consisting of modulation of the various translation factors (Figures 2, 3 and S3). Overall the parameter estimation was carried out over 212 different data points (steady states).

This model is described in the article:

Helena Firczuk, Shichina Kannambath, Jürgen Pahle, Amy Claydon, Robert Beynon, John Duncan, Hans Westerhoff, Pedro Mendes and John EG McCarthy
Molecular Systems Biology. 9:635

Abstract:

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • An in vivo control map for the eukaryotic mRNA translation machinery.
  • Firczuk H, Kannambath S, Pahle J, Claydon A, Beynon R, Duncan J, Westerhoff HV, Mendes P, McCarthy JE
  • Molecular Systems Biology , 0/ 2013 , Volume 9 , pages: 635 , PubMed ID: 23340841
  • School of Life Sciences, University of Warwick, Coventry, UK.
  • Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNA(i) to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5'untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5'UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.
Contributors
Pedro Mendes

Metadata information

is
BioModels Database MODEL1205190000
BioModels Database BIOMD0000000457
isDescribedBy
PubMed 23340841
isVersionOf
Gene Ontology translation

Curation status
Curated

Tags
Name Description Size Actions

Model files

BIOMD0000000457_url.xml SBML L2V4 representation of Firczuk2013 - Eukaryotic mRNA translation machinery 835.31 KB Preview | Download

Additional files

BIOMD0000000457.xpp Auto-generated XPP file 61.74 KB Preview | Download
BIOMD0000000457.sci Auto-generated Scilab file 60.43 KB Preview | Download
BIOMD0000000457-biopax3.owl Auto-generated BioPAX (Level 3) 608.07 KB Preview | Download
BIOMD0000000457-biopax2.owl Auto-generated BioPAX (Level 2) 396.34 KB Preview | Download
BIOMD0000000457.svg Auto-generated Reaction graph (SVG) 0.00 bytes Preview | Download
BIOMD0000000457.m Auto-generated Octave file 70.93 KB Preview | Download
BIOMD0000000457_urn.xml Auto-generated SBML file with URNs 843.45 KB Preview | Download
BIOMD0000000457.png Auto-generated Reaction graph (PNG) 0.00 bytes Preview | Download
BIOMD0000000457.vcml Auto-generated VCML file 1.04 MB Preview | Download
BIOMD0000000457.pdf Auto-generated PDF file 1.42 MB Preview | Download

  • Model originally submitted by : Pedro Mendes
  • Submitted: 19-May-2012 16:58:43
  • Last Modified: 21-Jun-2013 12:28:41
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 21-Jun-2013 12:28:41
    • Submitted by: Pedro Mendes
    • With comment: Current version of Firczuk2013 - Eukaryotic mRNA translation machinery
  • Version: 1 public model Download this version
    • Submitted on: 19-May-2012 16:58:43
    • Submitted by: Pedro Mendes
    • With comment: Original import of Translation
Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
(eIF2_GDP + eIF2B) => (eIF2_GDP_eIF2B)

([GDP; Eukaryotic translation initiation factor 2 subunit beta; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2 subunit gamma; eukaryotic translation initiation factor 2 complex] + [Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Translation initiation factor eIF-2B subunit epsilon; eukaryotic translation initiation factor 2B complex]) => ([GDP; Translation initiation factor eIF-2B subunit epsilon; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2 subunit gamma])
compartment_1*(k1*species_1*species_2-k2*species_3)

compartment_1*(k1*[GDP; Eukaryotic translation initiation factor 2 subunit beta; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2 subunit gamma; eukaryotic translation initiation factor 2 complex]*[Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Translation initiation factor eIF-2B subunit epsilon; eukaryotic translation initiation factor 2B complex]-k2*[GDP; Translation initiation factor eIF-2B subunit epsilon; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2 subunit gamma])
k2=34.8025; k1=1.96096E7
(eIF2_GDP_eIF2B) => (eIF2_GTP + eIF2B)

([GDP; Translation initiation factor eIF-2B subunit epsilon; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2 subunit gamma]) => ([eukaryotic translation initiation factor 2 complex; GTP; Eukaryotic translation initiation factor 2 subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Eukaryotic translation initiation factor 2 subunit alpha] + [Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Translation initiation factor eIF-2B subunit epsilon; eukaryotic translation initiation factor 2B complex])
compartment_1*(k1*species_3-k2*species_4*species_2)

compartment_1*(k1*[GDP; Translation initiation factor eIF-2B subunit epsilon; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2 subunit gamma]-k2*[eukaryotic translation initiation factor 2 complex; GTP; Eukaryotic translation initiation factor 2 subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Eukaryotic translation initiation factor 2 subunit alpha]*[Translation initiation factor eIF-2B subunit beta; Translation initiation factor eIF-2B subunit alpha; Translation initiation factor eIF-2B subunit delta; Translation initiation factor eIF-2B subunit gamma; Translation initiation factor eIF-2B subunit epsilon; eukaryotic translation initiation factor 2B complex])
k1=533.26; k2=3.97698
(eIF2_GTP + Met-tRNA) => (eIF2_GTP_Met-tRNA)

([eukaryotic translation initiation factor 2 complex; GTP; Eukaryotic translation initiation factor 2 subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Eukaryotic translation initiation factor 2 subunit alpha] + [tRNA(Met)]) => ([GTP; tRNA(Met); translation initiation ternary complex; eukaryotic translation initiation factor 2 complex])
compartment_1*(k1*species_4*species_5-k2*species_6)

compartment_1*(k1*[eukaryotic translation initiation factor 2 complex; GTP; Eukaryotic translation initiation factor 2 subunit gamma; Eukaryotic translation initiation factor 2 subunit beta; Eukaryotic translation initiation factor 2 subunit alpha]*[tRNA(Met)]-k2*[GTP; tRNA(Met); translation initiation ternary complex; eukaryotic translation initiation factor 2 complex])
k2=6.32998; k1=104798.0
(eIF4A + eIF4E_eIF4G_mRNA_Pab1) => (eIF4A_eIF4E_eIF4G_mRNA_Pab1)

([ATP-dependent RNA helicase eIF4A] + [messenger RNA; Eukaryotic initiation factor 4F subunit p130; Polyadenylate-binding protein, cytoplasmic and nuclear; Eukaryotic initiation factor 4F subunit p150; Eukaryotic translation initiation factor 4E]) => ([messenger RNA; Eukaryotic initiation factor 4F subunit p150; ATP-dependent RNA helicase eIF4A; Eukaryotic translation initiation factor 4E; Eukaryotic initiation factor 4F subunit p130])
compartment_1*(k1*species_24*species_23-k2*species_166)

compartment_1*(k1*[ATP-dependent RNA helicase eIF4A]*[messenger RNA; Eukaryotic initiation factor 4F subunit p130; Polyadenylate-binding protein, cytoplasmic and nuclear; Eukaryotic initiation factor 4F subunit p150; Eukaryotic translation initiation factor 4E]-k2*[messenger RNA; Eukaryotic initiation factor 4F subunit p150; ATP-dependent RNA helicase eIF4A; Eukaryotic translation initiation factor 4E; Eukaryotic initiation factor 4F subunit p130])
k2=2.38184; k1=307831.0
(80S_tRNA_19 + eEF3_GTP) => (80S_tRNA_eEF3_GTP_19)

([transfer RNA; cytosolic ribosome] + [GTP; Elongation factor 3A]) => ([GTP; alpha-aminoacyl-tRNA; Elongation factor 3A; cytosolic ribosome])
compartment_1*parameter_8*species_156*species_44

compartment_1*parameter_8*[transfer RNA; cytosolic ribosome]*[GTP; Elongation factor 3A]
parameter_8 = 2.24052E9
(80S_tRNA_17 + eEF3_GTP) => (80S_tRNA_eEF3_GTP_17)

([transfer RNA; cytosolic ribosome] + [GTP; Elongation factor 3A]) => ([alpha-aminoacyl-tRNA; GTP; Elongation factor 3A; cytosolic ribosome])
compartment_1*parameter_8*species_144*species_44

compartment_1*parameter_8*[transfer RNA; cytosolic ribosome]*[GTP; Elongation factor 3A]
parameter_8 = 2.24052E9
(80S_tRNA_eEF3_GTP_5) => (80S_5 + eEF3_GDP + tRNA)

([GTP; alpha-aminoacyl-tRNA; Elongation factor 3A; cytosolic ribosome]) => ([cytosolic ribosome] + [GDP; Elongation factor 3A] + [transfer RNA])
compartment_1*parameter_9*species_73

compartment_1*parameter_9*[GTP; alpha-aminoacyl-tRNA; Elongation factor 3A; cytosolic ribosome]
parameter_9 = 72911.6740026381
(80S_tRNA_eEF3_GTP_7) => (80S_7 + eEF3_GDP + tRNA)

([alpha-aminoacyl-tRNA; GTP; Elongation factor 3A; cytosolic ribosome]) => ([cytosolic ribosome] + [GDP; Elongation factor 3A] + [transfer RNA])
compartment_1*parameter_9*species_85

compartment_1*parameter_9*[alpha-aminoacyl-tRNA; GTP; Elongation factor 3A; cytosolic ribosome]
parameter_9 = 72911.6740026381
Curator's comment:
(added: 27 Feb 2013, 18:12:07, updated: 27 Feb 2013, 18:12:07)
Figure 2g (k26 versus free ribosome) is reproduced here, in concentrations. The data were obtained by simulating the model using Copasi v4.8 (Build 35). The plot was generated using Gnuplot.