Global stabilization of the transcriptome in mitotic cells
Ekaterina Khalizeva1,2, Arash Latifkar1,2,3, Kehui Xiang1,2,3
1Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
The EMBO Journal
|April 9, 2026
Summary
Mammalian cells stabilize their transcriptome during prolonged mitotic arrest, increasing mRNA half-lives over fourfold. This crucial adaptation, dependent on PABPC1&4, prevents mRNA depletion without new transcription, ensuring cell viability.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cell division errors can cause prolonged mitotic arrest in mammalian cells.
- Mitosis requires continued translation for viability despite minimal transcription.
- Maintaining mRNA levels during mitotic arrest necessitates adaptations in gene expression.
Purpose of the Study:
- To investigate how mammalian cells maintain their transcriptome during extended mitotic delays.
- To identify the mechanisms responsible for mRNA stability during mitosis.
- To determine the role of specific proteins in mitotic mRNA homeostasis.
Main Methods:
- Measurement of mRNA half-lives in interphase versus mitotic arrest.
- Analysis of poly(A) tail-length dynamics during mitosis.
- Assessment of siRNA-mediated mRNA degradation during mitotic arrest.
- Depletion of PABPC1&4 using siRNA and subsequent analysis of mRNA stability and mitotic arrest.
Main Results:
- Global stabilization of the transcriptome during prolonged mitotic arrest was observed.
- Median mRNA half-lives increased more than fourfold during mitotic arrest compared to interphase.
- Mitotic arrest induced changes in poly(A) tail length, suggesting repressed deadenylation.
- siRNA-directed mRNA degradation machinery remained active during mitotic arrest.
- Depletion of PABPC1&4 compromised mRNA stability and the ability to maintain mitotic arrest.
Conclusions:
- Mammalian cells globally stabilize their transcriptome during prolonged mitotic arrest.
- Mitotic mRNA stabilization is a critical adaptation for cell viability, buffering mRNA levels in the absence of transcription.
- PABPC1&4 plays a vital role in maintaining mitotic mRNA stability and supporting prolonged mitotic arrest.
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