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A hypothesis to explain why translation inhibitors stabilize mRNAs in mammalian cells: mRNA stability and mitosis
1McArdle Laboratory for Cancer Research, University of Wisconsin- Madison 53706, USA. ross@oncology.wisc.edu
Abstract:
Protein synthesis inhibitors prolong the half-lives of most mRNAs at least fourfold in the somatic cells of higher eukaryotes and in yeast cells. Some mRNAs are stabilized because the inhibitors affect mRNA-specific regulatory factors; however, hundreds or thousands of other mRNAs are probably stabilized by a common mechanism. We propose that mRNA stabilization in cells treated with a translation inhibitor reflects a physiological process that occurs during each mitosis and is important for cell survival. Transcription and translation rates decline drastically during a 1-2 hour interval of mitosis. We hypothesize that translational repression during this interval somehow inactivates a critical component of the mRNA degradation machinery. As a result, mRNA half-lives are prolonged during the interval when transcription is repressed. If labile mRNAs were not stabilized during mitosis they, and perhaps also the labile proteins they encode, would be depleted as the cell entered G1 phase, with deleterious consequences. Stabilization during mitosis, or in response to translation inhibitors, thus preserves the capacity of the cell to synthesize essential proteins as it enters G1 or recovers from inhibitor treatment. mRNA stabilization might serve a similar purpose during starvation or any stress negatively affecting translation.
Insights
Protein synthesis inhibitors stabilize messenger RNAs (mRNAs) by a common mechanism, likely during mitosis. This process protects cells by preserving essential protein production during critical periods.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Protein synthesis inhibitors significantly extend messenger RNA (mRNA) half-lives in eukaryotic cells.
- While some mRNA stabilization is due to specific regulatory factors, a common mechanism likely affects numerous mRNAs.
Purpose of the Study:
- To investigate the hypothesis that mRNA stabilization observed with translation inhibitors reflects a conserved physiological process during mitosis.
- To understand the role of this stabilization in cell survival and protein synthesis capacity.
Main Methods:
- The study proposes a mechanism involving translational repression during mitosis.
- This repression is hypothesized to inactivate mRNA degradation machinery, leading to mRNA stabilization.
Main Results:
- mRNA half-lives are prolonged during mitosis due to repressed transcription and translation.
- This stabilization prevents the depletion of labile mRNAs and their encoded proteins as cells enter the G1 phase.
Conclusions:
- mRNA stabilization during mitosis, or induced by translation inhibitors, is crucial for maintaining cellular protein synthesis capacity.
- This mechanism is vital for cell survival, particularly during periods of stress like starvation or mitotic arrest.