A model for competition for ribosomes in the cell

Area of Science:

• Molecular Biology
• Systems Biology
• Biophysics

Background:

• Mammalian cells contain vast numbers of mRNA molecules and ribosomes, necessitating simultaneous translation.
• Competition for a finite pool of ribosomes among numerous mRNA molecules creates complex correlations.
• Understanding these simultaneous translation dynamics is crucial for gene expression regulation, evolution, and synthetic biology.

Purpose of the Study:

• To develop and analyze a dynamical model for large-scale simultaneous mRNA translation and ribosome competition.
• To investigate the steady-state interactions and emergent properties of interconnected translation systems.
• To explore how changes in translation rates and mRNA length affect overall protein production.

Main Methods:

• Development of a general dynamical model combining multiple ribosome flow models (RFMs).
• Interconnection of RFMs through a shared pool of free ribosomes.
• Analysis of system convergence to steady state and entrainment to time-varying rates.

Main Results:

• The model system consistently converges to a steady state and exhibits phase locking to periodic rate variations.
• Altering translation rates in one mRNA has both local (self-enhancement) and global (coordinated changes in others) effects.
• Increased mRNA length universally decreases the production rates of all mRNAs in the system.

Conclusions:

• Simultaneous translation dynamics are complex, with significant cross-regulatory effects between mRNA molecules.
• Codon translation rates have more intricate impacts on protein production than previously assumed.
• mRNA length is a critical factor influencing the efficiency of simultaneous translation processes.