Ribosome Sequestration
Also known as: ribosome titration, ribosome trapping
The depletion of free ribosomes by highly expressed mRNAs, reducing translation capacity available for other transcripts in the cell.
Ribosome Sequestration is the phenomenon where highly expressed mRNAs capture a disproportionate share of the cellular ribosome pool, depleting the free ribosome concentration and reducing translation of all other transcripts 1.
How It Works
Cells contain a finite number of ribosomes, typically 10,000-70,000 per cell in E. coli depending on growth rate. Each actively translating ribosome is engaged with an mRNA and unavailable for new translation initiation events. When a heterologous gene is expressed at high levels, its mRNAs can capture a substantial fraction of the total ribosome pool.
As free ribosome concentration drops, translation initiation rates for all mRNAs decrease proportionally. This global depression of translation affects both synthetic circuit components and essential host genes. The effect is particularly severe for mRNAs with weak RBS sequences, which are more sensitive to reduced ribosome availability.
Ribosome sequestration can also be used as a deliberate design strategy. Engineered non-coding RNAs or decoy mRNAs can sequester ribosomes to implement translational regulation. Small RNA-based ribosome sponges provide tunable control over free ribosome concentration and global expression levels.
Computational Considerations
Whole-cell models of ribosome allocation explicitly track the distribution of ribosomes across all mRNA species, computing the steady-state free ribosome concentration from the total ribosome budget. These models predict how introducing new genes will affect expression of existing genes through ribosome competition. Active learning approaches optimize expression systems by exploring the trade-off between heterologous expression and host viability 2.
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Whole-cell models track ribosome allocation across all mRNAs to predict how sequestration by heterologous genes depresses native and circuit gene expression.