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Autoregulation of Transcription and Translation: A Qualitative Analysis

The regulation of both mRNA transcription and translation by down-stream gene products allows for a range of rich dynamical behaviours (e.g. homeostatic, oscillatory, excitability and intermittent solutions). Here, qualitative analysis is applied to an existing model of a gene regulatory network in...

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Autor principal: Murray, Philip J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219895/
https://www.ncbi.nlm.nih.gov/pubmed/37233955
http://dx.doi.org/10.1007/s11538-023-01143-6
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author Murray, Philip J.
author_facet Murray, Philip J.
author_sort Murray, Philip J.
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description The regulation of both mRNA transcription and translation by down-stream gene products allows for a range of rich dynamical behaviours (e.g. homeostatic, oscillatory, excitability and intermittent solutions). Here, qualitative analysis is applied to an existing model of a gene regulatory network in which a protein dimer inhibits its own transcription and upregulates its own translation rate. It is demonstrated that the model possesses a unique steady state, conditions are derived under which limit cycle solutions arise and estimates are provided for the oscillator period in the limiting case of a relaxation oscillator. The analysis demonstrates that oscillations can arise only if mRNA is more stable than protein and the effect of nonlinear translation inhibition is sufficiently strong. Moreover, it is shown that the oscillation period can vary non-monotonically with transcription rate. Thus the proposed framework can provide an explanation for observed species-specific dependency of segmentation clock period on Notch signalling activity. Finally, this study facilitates the application of the proposed model to more general biological settings where post transcriptional regulation effects are likely important.
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spelling pubmed-102198952023-05-28 Autoregulation of Transcription and Translation: A Qualitative Analysis Murray, Philip J. Bull Math Biol Original Article The regulation of both mRNA transcription and translation by down-stream gene products allows for a range of rich dynamical behaviours (e.g. homeostatic, oscillatory, excitability and intermittent solutions). Here, qualitative analysis is applied to an existing model of a gene regulatory network in which a protein dimer inhibits its own transcription and upregulates its own translation rate. It is demonstrated that the model possesses a unique steady state, conditions are derived under which limit cycle solutions arise and estimates are provided for the oscillator period in the limiting case of a relaxation oscillator. The analysis demonstrates that oscillations can arise only if mRNA is more stable than protein and the effect of nonlinear translation inhibition is sufficiently strong. Moreover, it is shown that the oscillation period can vary non-monotonically with transcription rate. Thus the proposed framework can provide an explanation for observed species-specific dependency of segmentation clock period on Notch signalling activity. Finally, this study facilitates the application of the proposed model to more general biological settings where post transcriptional regulation effects are likely important. Springer US 2023-05-26 2023 /pmc/articles/PMC10219895/ /pubmed/37233955 http://dx.doi.org/10.1007/s11538-023-01143-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Murray, Philip J.
Autoregulation of Transcription and Translation: A Qualitative Analysis
title Autoregulation of Transcription and Translation: A Qualitative Analysis
title_full Autoregulation of Transcription and Translation: A Qualitative Analysis
title_fullStr Autoregulation of Transcription and Translation: A Qualitative Analysis
title_full_unstemmed Autoregulation of Transcription and Translation: A Qualitative Analysis
title_short Autoregulation of Transcription and Translation: A Qualitative Analysis
title_sort autoregulation of transcription and translation: a qualitative analysis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219895/
https://www.ncbi.nlm.nih.gov/pubmed/37233955
http://dx.doi.org/10.1007/s11538-023-01143-6
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