Abstract
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.
Original language | English |
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Article number | 57 |
Number of pages | 27 |
Journal | Bulletin of Mathematical Biology |
Volume | 85 |
Issue number | 7 |
DOIs | |
Publication status | Published - 26 May 2023 |
Keywords
- Models, Biological
- Mathematical Concepts
- Transcription, Genetic
- Homeostasis
- RNA, Messenger/genetics
- Translation
- Molecular oscillator
- Relaxation oscillator
- Transcription
- Notch signalling
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General Environmental Science
- General Mathematics
- General Biochemistry,Genetics and Molecular Biology
- General Neuroscience
- Pharmacology
- Computational Theory and Mathematics
- Immunology