Signaling Pathways Differentially Affect RNA Polymerase II Initiation, Pausing, and Elongation Rate in Cells
Open accessAbstract
RNA polymerase II (Pol II) transcribes hundreds of kilobases of DNA, limiting the production of mRNAs and lncRNAs. We used global run-on sequencing (GRO-seq) to measure the rates of transcription by Pol II following gene activation. Elongation rates vary as much as 4-fold at different genomic loci and in response to two distinct cellular signaling pathways (i.e., 17β-estradiol [E2] and TNF-α). The rates are slowest near the promoter and increase during the first ~15 kb transcribed. Gene body elongation rates correlate with Pol II density, resulting in systematically higher rates of transcript production at genes with higher Pol II density. Pol II dynamics following short inductions indicate that E2 stimulates gene expression by increasing Pol II initiation, whereas TNF-α reduces Pol II residence time at pause sites. Collectively, our results identify previously uncharacterized variation in the rate of transcription and highlight elongation as an important, variable, and regulated rate-limiting step during transcription.
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Genome-wide techniques showed in various human cell lines that average RNA Pol II speed ranges between 1.25 kb/min and 3.5 kb/min.
“All these techniques showed in various human cell lines that the average RNA Pol II speed ranges between 1.25 kb/min and 3.5 kb/min (Danko et al, 2013; Fuchs et al, 2014b; Jonkers et al, 2014; Saponaro et al, 2014; Veloso et al, 2014; Liang et al, 2018; Baluapuri et al, 2019; Gregersen et al, 2020).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Danko et al, 2013
The Results section, “Comparing Rates of Transcription in MCF-7 and AC16 Cells” (page unavailable), reports genome-scale Pol II measurements in two human cell lines, with median rates of 2.1 and 2.80 kb/min. It does not establish the cited sentence’s 1.25–3.5 kb/min range of average speeds; its reported middle-90% range for individual genes in MCF-7 cells is 0.37–3.57 kb/min. (LLM, conf=0.85)
Experimental — accuracy not yet measuredRNA Pol II speed is highly variable within individual genes, as RNA Pol II accelerates while traveling throughout the gene body, starting at 0.5 kb/min in the first 10-15 kb and accelerating up to 2-4 kb/min downstream.
“RNA Pol II speed was furthermore also shown to be highly variable within individual genes, as RNA Pol II accelerates while traveling throughout the gene body, starting at 0.5 kb/min in the first 10–15 kb and accelerating up to 2–4 kb/min downstream (Danko et al, 2013; Fuchs et al, 2014b; Jonkers et al, 2014; Saponaro et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Danko et al, 2013
The Results section, “Comparing Pol II Elongation Rates During Early and Late Transcription” (page unavailable), reports that rates increase within genes, particularly over the first ~10–15 kb. It does not establish the claimed progression from 0.5 kb/min in that region to 2–4 kb/min downstream; the reported rate range describes variation across genes, not those two positions within a gene. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMeasured transcription speed is extremely variable between genes, with RNA Pol II velocity varying from 0.37 kb/min to 3.57 kb/min for individual genes.
“Contrary to what had been initially shown for a few genes (Singh & Padgett, 2009; Wada et al, 2009), the measured transcription speed was found to be extremely variable between genes, with RNA Pol II velocity varying from 0.37 kb/min to 3.57 kb/min for individual genes (Danko et al, 2013).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Danko et al, 2013
The Results section, “Comparing Rates of Transcription in MCF-7 and AC16 Cells,” reports substantial variation between genes and gives the cited 0.37–3.57 kb/min range. That range applies to the middle 90% of 140 E2-upregulated genes measured in MCF-7 cells, not an unqualified range for individual genes generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRNA Pol II velocity can differ by as much as 25-40% on individual genes in different cell lines and in response to diverse signaling pathways.
“However, Danko et al (2013) found that RNA Pol II velocity can differ by as much as 25–40% on individual genes in different cell lines and in response to diverse signaling pathways.”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Danko et al, 2013
Genes with the highest measured RNA Pol II velocity generate more mRNAs.
“Indeed, genes with the highest measured RNA Pol II velocity have been shown to generate more mRNAs (Danko et al, 2013; Jonkers et al, 2014; Cohen et al, 2018).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Danko et al, 2013
RNA Pol II velocity differs by as much as 25-40% on individual genes stimulated by diverse signaling pathways in different cell lines.
“First, RNA Pol II velocity differs by as much as 25–40% on individual genes stimulated by diverse signaling pathways in different cell lines (Danko et al, 2013).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Danko et al, 2013
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Chromatin, DNA structure and alternative splicing
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- Authors
- Danko, C. G., Hah, N., Luo, X., Martins, A. L., Core, L., Lis, J. T., Siepel, A., & Kraus, W. L.
- Affiliations
- Cornell University (US)
- Corresponding author
- Kraus, W. Lee
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 50
- Issue
- 2
- Pages
- 212-222
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3640649
- OpenAlex
- W2016349604
- Cited by
- 333
- References
- 38
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 21 · 2023: 15 · 2022: 20 · 2021: 34 · 2020: 21 · 2019: 27 · 2018: 32 · 2017: 25 · 2016: 34 · 2015: 33 · 2014: 29 · 2013: 16
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-06-06)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- U.S. Department of Defense
- Pharmaceutical Research and Manufacturers of America Foundation
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM025232, R37GM025232, GM-25232)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK058110, R01DK058110)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD052471)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- RNA polymerase II, transcription elongation, transcription initiation, RNA polymerase II pausing, elongation rate, estradiol, TNF-α, gene activation, pause sites, gene body, signaling pathways, transcriptional regulation
- MeSH terms
- Estradiol, Humans, Kinetics, Promoter Regions, Genetic, RNA Polymerase II, RNA, Messenger, Transcription Factors, Transcription, Genetic, Tumor Necrosis Factor-alpha, Signal Transduction, Transcriptional Activation, Transcription Initiation Site, Transcriptome, Transcription Initiation, Genetic, MCF-7 Cells
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