Auto-Regulation of Transcription and Translation: Oscillations, Excitability and Intermittency.

Area of Science:

• Molecular Biology
• Systems Biology
• Biophysics

Background:

• Hes/Her proteins are transcriptional repressors in the Notch signaling pathway.
• Autoinhibition of transcription is known to generate homeostasis and oscillations, especially with delays.
• Previous models often simplified translation as a linear, unregulated process.

Purpose of the Study:

• To develop a mathematical model incorporating nonlinear translation regulation alongside transcriptional autoinhibition.
• To explore the dynamical behaviors arising from this combined regulatory mechanism.
• To identify experimental strategies for detecting dual transcriptional and translational autoregulation.

Main Methods:

• Development of a novel mathematical model.
• Analysis of nonlinear dynamical behaviors.
• Simulation of system dynamics under varying regulatory conditions.

Main Results:

• The model demonstrates that nonlinear translation regulation, combined with transcriptional autoinhibition, can produce complex dynamics like excitability, homeostasis, oscillations, and intermittency, even without time delays.
• This integrated regulation offers a broader spectrum of behaviors compared to models with only transcriptional autoregulation.
• Specific experimental signatures for detecting combined autoregulation are proposed.

Conclusions:

• Nonlinear regulation of translation significantly expands the potential dynamic repertoire of Hes/Her gene systems within Notch signaling.
• Considering both transcriptional and translational control provides a more comprehensive understanding of biological network behavior.
• The proposed experiments can validate the model's predictions and elucidate the role of translational control in gene regulatory networks.