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3’-5’ crosstalk contributes to transcriptional bursting
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Cavallaro, Massimo, Walsh, Mark D., Jones, Matt, Teahan, James, Tiberi, Simone, Finkenstädt, Bärbel and Hebenstreit, Daniel (2021) 3’-5’ crosstalk contributes to transcriptional bursting. Genome Biology, 22 . 56. doi:10.1186/s13059-020-02227-5 ISSN 1474-7596.
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Official URL: https://doi.org/10.1186/s13059-020-02227-5
Abstract
Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to “transcriptional bursting” have been identified, usually classified as intrinsic, i.e., local to single genes, or extrinsic, relating to the macroscopic state of the cell. However, each factor only accounts partially for the observed phenomenon, and some possible contributors have not been explored yet. We investigate processes at the 3’ and 5’ ends of a gene that enable reinitiation of transcription upon termination. Using an interdisciplinary approach, we measured the transcriptional bursting at a set of inducible transgenes with sufficient accuracy and precision to unveil significant patterns. We find that perturbation of polymerase shuttling typically reduces the average burst size and increases the burst frequency, thus limiting transcriptional noise. The observed noise patterns are reproduced by a generative model that captures major characteristics of the polymerase flux between a gene and a phase-separated compartment.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QA Mathematics Q Science > QH Natural history |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Science > Statistics |
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| Library of Congress Subject Headings (LCSH): | Gene regulatory networks -- Mathematical models, Gene expression, Monte Carlo method, Bayesian statistical decision theory | |||||||||
| Journal or Publication Title: | Genome Biology | |||||||||
| Publisher: | BioMed Central Ltd. | |||||||||
| ISSN: | 1474-7596 | |||||||||
| Official Date: | 4 February 2021 | |||||||||
| Dates: |
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| Volume: | 22 | |||||||||
| Article Number: | 56 | |||||||||
| DOI: | 10.1186/s13059-020-02227-5 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 4 December 2020 | |||||||||
| Date of first compliant Open Access: | 10 March 2021 | |||||||||
| RIOXX Funder/Project Grant: |
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