The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Kinetic competition during the transcription cycle results in stochastic RNA processing
Open accessAbstract
Synthesis of mRNA in eukaryotes involves the coordinated action of many enzymatic processes, including initiation, elongation, splicing, and cleavage. Kinetic competition between these processes has been proposed to determine RNA fate, yet such coupling has never been observed in vivo on single transcripts. In this study, we use dual-color single-molecule RNA imaging in living human cells to construct a complete kinetic profile of transcription and splicing of the β-globin gene. We find that kinetic competition results in multiple competing pathways for pre-mRNA splicing. Splicing of the terminal intron occurs stochastically both before and after transcript release, indicating there is not a strict quality control checkpoint. The majority of pre-mRNAs are spliced after release, while diffusing away from the site of transcription. A single missense point mutation (S34F) in the essential splicing factor U2AF1 which occurs in human cancers perturbs this kinetic balance and defers splicing to occur entirely post-release.
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Cites
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Self-citationInsights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins
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Frequent pathway mutations of splicing machinery in myelodysplasia
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Bentley, D. L. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3662 · Cited by 828
Nascent transcript sequencing visualizes transcription at nucleotide resolution
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From Silencing to Gene Expression
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Cited by
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Single-cell nascent RNA sequencing unveils coordinated global transcription
Mahat, D. B., Tippens, N. D., Martin-Rufino, J. D., Waterton, S. K., Fu, J., Blatt, S. E., & Sharp, P. A. (2024) · Nature · doi:10.1038/s41586-024-07517-7 · Cited by 131
Perfect timing: splicing and transcription rates in living cells
Alpert, T., Herzel, L., & Neugebauer, K. M. (2017) · WIREs RNA · doi:10.1002/wrna.1401 · Cited by 99
Taylor, T., Sikorska, N., Shchuka, V. M., Chahar, S., Ji, C., Macpherson, N. N., Moorthy, S. D., de Kort, M. A. C., Mullany, S., Khader, N., et al. (2022) · Genes & Development · doi:10.1101/gad.349489.122 · Cited by 45
Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics
Platania, A., Erb, C., Barbieri, M., Molcrette, B., Grandgirard, E., de Kort, M. A. C., Pomp, W., Meaburn, K., Taylor, T., Shchuka, V. M., et al. (2024) · Science Advances · doi:10.1126/sciadv.adq0987 · Cited by 40
Metadata
- Authors
- Coulon, A., Ferguson, M. L., de Turris, V., Palangat, M., Chow, C. C., & Larson, D. R.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2014-10-01
- Volume
- 3
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2129218346
- Cited by
- 228
- References
- 14
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- gold
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- Coulon, A., Ferguson, M. L., de Turris, V., Palangat, M., Chow, C. C., & Larson, D. R. (2014). Kinetic competition during the transcription cycle results in stochastic RNA processing. eLife. https://doi.org/10.7554/elife.03939
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