The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription.
Gene transcription is a noisy process, and cell division cycle is an important source of gene transcription noise. In this work, we develop a mathematical approach by coupling transcription kinetics with cell division cycles to delineate how they are combined to regulate transcription output and noi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-04-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1007017 |
| _version_ | 1797351475613007872 |
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| author | Qiwen Sun Feng Jiao Genghong Lin Jianshe Yu Moxun Tang |
| author_facet | Qiwen Sun Feng Jiao Genghong Lin Jianshe Yu Moxun Tang |
| author_sort | Qiwen Sun |
| collection | DOAJ |
| description | Gene transcription is a noisy process, and cell division cycle is an important source of gene transcription noise. In this work, we develop a mathematical approach by coupling transcription kinetics with cell division cycles to delineate how they are combined to regulate transcription output and noise. In view of gene dosage, a cell cycle is divided into an early stage [Formula: see text] and a late stage [Formula: see text]. The analytical forms for the mean and the noise of mRNA numbers are given in each stage. The analysis based on these formulas predicts precisely the fold change r* of mRNA numbers from [Formula: see text] to [Formula: see text] measured in a mouse embryonic stem cell line. When transcription follows similar kinetics in both stages, r* buffers against DNA dosage variation and r* ∈ (1, 2). Numerical simulations suggest that increasing cell cycle durations up-regulates transcription with less noise, whereas rapid stage transitions induce highly noisy transcription. A minimization of the transcription noise is observed when transcription homeostasis is attained by varying a single kinetic rate. When the transcription level scales with cellular volume, either by reducing the transcription burst frequency or by increasing the burst size in [Formula: see text], the noise shows only a minor variation over a wide range of cell cycle stage durations. The reduction level in the burst frequency is nearly a constant, whereas the increase in the burst size is conceivably sensitive, when responding to a large random variation of the cell cycle durations and the gene duplication time. |
| first_indexed | 2024-03-08T13:01:00Z |
| format | Article |
| id | doaj.art-23bd006776604348a53b957b83afaef0 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-03-08T13:01:00Z |
| publishDate | 2019-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-23bd006776604348a53b957b83afaef02024-01-19T05:36:50ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582019-04-01154e100701710.1371/journal.pcbi.1007017The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription.Qiwen SunFeng JiaoGenghong LinJianshe YuMoxun TangGene transcription is a noisy process, and cell division cycle is an important source of gene transcription noise. In this work, we develop a mathematical approach by coupling transcription kinetics with cell division cycles to delineate how they are combined to regulate transcription output and noise. In view of gene dosage, a cell cycle is divided into an early stage [Formula: see text] and a late stage [Formula: see text]. The analytical forms for the mean and the noise of mRNA numbers are given in each stage. The analysis based on these formulas predicts precisely the fold change r* of mRNA numbers from [Formula: see text] to [Formula: see text] measured in a mouse embryonic stem cell line. When transcription follows similar kinetics in both stages, r* buffers against DNA dosage variation and r* ∈ (1, 2). Numerical simulations suggest that increasing cell cycle durations up-regulates transcription with less noise, whereas rapid stage transitions induce highly noisy transcription. A minimization of the transcription noise is observed when transcription homeostasis is attained by varying a single kinetic rate. When the transcription level scales with cellular volume, either by reducing the transcription burst frequency or by increasing the burst size in [Formula: see text], the noise shows only a minor variation over a wide range of cell cycle stage durations. The reduction level in the burst frequency is nearly a constant, whereas the increase in the burst size is conceivably sensitive, when responding to a large random variation of the cell cycle durations and the gene duplication time.https://doi.org/10.1371/journal.pcbi.1007017 |
| spellingShingle | Qiwen Sun Feng Jiao Genghong Lin Jianshe Yu Moxun Tang The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription. PLoS Computational Biology |
| title | The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription. |
| title_full | The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription. |
| title_fullStr | The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription. |
| title_full_unstemmed | The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription. |
| title_short | The nonlinear dynamics and fluctuations of mRNA levels in cell cycle coupled transcription. |
| title_sort | nonlinear dynamics and fluctuations of mrna levels in cell cycle coupled transcription |
| url | https://doi.org/10.1371/journal.pcbi.1007017 |
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