A mathematical modelling framework for elucidating the role of feedback control in translation termination

Eric de Silva, J Krishnan, Russell Betney, Ian Stansfield

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Translation is the final stage of gene expression where messenger RNA is used as a template for protein polymerization from appropriate amino acids. Release of the completed protein requires a release factor protein acting at the termination/stop codon to liberate it. In this paper we focus on a complex feedback control mechanism involved in the translation and synthesis of release factor proteins, which has been observed in different systems. These release factor proteins are involved in the termination stage of their own translation. Further, mutations in the release factor gene can result in a premature stop codon. In this case translation can result either in early termination and the production of a truncated protein or readthrough of the premature stop codon and production of the complete release factor protein. Thus during translation of the release factor mRNA containing a premature stop codon, the full length protein negatively regulates its production by its action on a premature stop codon, while positively regulating its production by its action on the regular stop codon. This paper develops a mathematical modelling framework to investigate this complex feedback control system involved in translation. A series of models is established to carefully investigate the role of individual mechanisms and how they work together. The steady state and dynamic behaviour of the resulting models are examined both analytically and numerically.
Original languageEnglish
Pages (from-to)808-821
Number of pages14
JournalJournal of Theoretical Biology
Volume264
Issue number3
Early online date20 Feb 2010
DOIs
Publication statusPublished - 7 Jun 2010

Fingerprint

stop codon
Mathematical Modeling
Termination
Feedback Control
translation (genetics)
Feedback control
mathematical models
Proteins
Protein
Nonsense Codon
Terminator Codon
proteins
Messenger RNA
Early Termination
Framework
Polymerization
Feedback Systems
messenger RNA
Gene expression
polymerization

Keywords

  • Feedback control
  • Complex control system
  • Translation termination
  • Dynamic analysis
  • Control structure

Cite this

A mathematical modelling framework for elucidating the role of feedback control in translation termination. / de Silva, Eric; Krishnan, J; Betney, Russell; Stansfield, Ian.

In: Journal of Theoretical Biology, Vol. 264, No. 3, 07.06.2010, p. 808-821.

Research output: Contribution to journalArticle

@article{9ec12456a7af4063adf69da692677e3f,
title = "A mathematical modelling framework for elucidating the role of feedback control in translation termination",
abstract = "Translation is the final stage of gene expression where messenger RNA is used as a template for protein polymerization from appropriate amino acids. Release of the completed protein requires a release factor protein acting at the termination/stop codon to liberate it. In this paper we focus on a complex feedback control mechanism involved in the translation and synthesis of release factor proteins, which has been observed in different systems. These release factor proteins are involved in the termination stage of their own translation. Further, mutations in the release factor gene can result in a premature stop codon. In this case translation can result either in early termination and the production of a truncated protein or readthrough of the premature stop codon and production of the complete release factor protein. Thus during translation of the release factor mRNA containing a premature stop codon, the full length protein negatively regulates its production by its action on a premature stop codon, while positively regulating its production by its action on the regular stop codon. This paper develops a mathematical modelling framework to investigate this complex feedback control system involved in translation. A series of models is established to carefully investigate the role of individual mechanisms and how they work together. The steady state and dynamic behaviour of the resulting models are examined both analytically and numerically.",
keywords = "Feedback control, Complex control system, Translation termination, Dynamic analysis, Control structure",
author = "{de Silva}, Eric and J Krishnan and Russell Betney and Ian Stansfield",
note = "A paid open access option is available for this journal. Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists Set statement to accompany deposit Published source must be acknowledged Must link to journal home page or articles' DOI Publisher's version/PDF cannot be used Articles in some journals can be made Open Access on payment of additional charge NIH Authors articles will be submitted to PubMed Central after 12 month Authors who are required to deposit in subject-based repositories may also use Sponsorship Option",
year = "2010",
month = "6",
day = "7",
doi = "10.1016/j.jtbi.2010.01.015",
language = "English",
volume = "264",
pages = "808--821",
journal = "Journal of Theoretical Biology",
issn = "0022-5193",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - A mathematical modelling framework for elucidating the role of feedback control in translation termination

AU - de Silva, Eric

AU - Krishnan, J

AU - Betney, Russell

AU - Stansfield, Ian

N1 - A paid open access option is available for this journal. Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists Set statement to accompany deposit Published source must be acknowledged Must link to journal home page or articles' DOI Publisher's version/PDF cannot be used Articles in some journals can be made Open Access on payment of additional charge NIH Authors articles will be submitted to PubMed Central after 12 month Authors who are required to deposit in subject-based repositories may also use Sponsorship Option

PY - 2010/6/7

Y1 - 2010/6/7

N2 - Translation is the final stage of gene expression where messenger RNA is used as a template for protein polymerization from appropriate amino acids. Release of the completed protein requires a release factor protein acting at the termination/stop codon to liberate it. In this paper we focus on a complex feedback control mechanism involved in the translation and synthesis of release factor proteins, which has been observed in different systems. These release factor proteins are involved in the termination stage of their own translation. Further, mutations in the release factor gene can result in a premature stop codon. In this case translation can result either in early termination and the production of a truncated protein or readthrough of the premature stop codon and production of the complete release factor protein. Thus during translation of the release factor mRNA containing a premature stop codon, the full length protein negatively regulates its production by its action on a premature stop codon, while positively regulating its production by its action on the regular stop codon. This paper develops a mathematical modelling framework to investigate this complex feedback control system involved in translation. A series of models is established to carefully investigate the role of individual mechanisms and how they work together. The steady state and dynamic behaviour of the resulting models are examined both analytically and numerically.

AB - Translation is the final stage of gene expression where messenger RNA is used as a template for protein polymerization from appropriate amino acids. Release of the completed protein requires a release factor protein acting at the termination/stop codon to liberate it. In this paper we focus on a complex feedback control mechanism involved in the translation and synthesis of release factor proteins, which has been observed in different systems. These release factor proteins are involved in the termination stage of their own translation. Further, mutations in the release factor gene can result in a premature stop codon. In this case translation can result either in early termination and the production of a truncated protein or readthrough of the premature stop codon and production of the complete release factor protein. Thus during translation of the release factor mRNA containing a premature stop codon, the full length protein negatively regulates its production by its action on a premature stop codon, while positively regulating its production by its action on the regular stop codon. This paper develops a mathematical modelling framework to investigate this complex feedback control system involved in translation. A series of models is established to carefully investigate the role of individual mechanisms and how they work together. The steady state and dynamic behaviour of the resulting models are examined both analytically and numerically.

KW - Feedback control

KW - Complex control system

KW - Translation termination

KW - Dynamic analysis

KW - Control structure

U2 - 10.1016/j.jtbi.2010.01.015

DO - 10.1016/j.jtbi.2010.01.015

M3 - Article

VL - 264

SP - 808

EP - 821

JO - Journal of Theoretical Biology

JF - Journal of Theoretical Biology

SN - 0022-5193

IS - 3

ER -