Rates of in situ transcription and splicing in large human genes

Singh, Jarnail; Padgett, Richard A

doi:10.1038/nsmb.1666

Cited by 487RNA Research and SplicingGenomics and Chromatin DynamicsRNA and protein synthesis mechanisms

Rates of in situ transcription and splicing in large human genes

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Singh, Jarnail, Padgett, Richard A·2009·Nature Structural & Molecular Biology

DOI 10.1038/nsmb.1666PMC PMC2783620

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Abstract

Transcription and splicing must proceed over genomic distances of hundreds of kilobases in many human genes. However, the rates and mechanisms of these processes are poorly understood. We have used the compound 5,6-dichlorobenzimidazole 1-beta-D-ribofuranoside (DRB), which reversibly blocks gene transcription in vivo, combined with quantitative RT-PCR to analyze the transcription and RNA processing of several long human genes. We found that the rate of RNA polymerase II transcription over long genomic distances is about 3.8 kb min(-1) and is similar whether transcribing long introns or exon-rich regions. We also determined that co-transcriptional pre-mRNA splicing of U2-dependent introns occurs within 5-10 min of synthesis, irrespective of intron length between 1 kb and 240 kb. Similarly, U12-dependent introns were co-transcriptionally spliced within 10 min of synthesis, confirming that these introns are spliced within the nuclear compartment. These results show that the expression of large genes is unexpectedly rapid and efficient.

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Other studies have found no relationship between RNA Pol II speed and expression levels.
“However, other studies have found no relationship between RNA Pol II speed and expression levels (Singh & Padgett, 2009; Fukaya et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Singh & Padgett, 2009
The Discussion reports that genes with substantially different estimated expression levels had similar apparent elongation rates. It concludes only that, within the limits of its measurements and the genes studied, there did not appear to be a strong relationship between elongation rate and transcriptional activity; the claim's unqualified 'no relationship' is stronger. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Transcription speed on individual genes is overall well conserved between cell lines.
“In addition, comparison of transcription speed between different cell lines showed that transcription speed on individual genes is overall well conserved between cell lines (Singh & Padgett, 2009; Veloso et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Singh & Padgett, 2009

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Authors: Singh, J., & Padgett, R. A.
Affiliations: Cleveland Clinic (US)
Corresponding author: Padgett, Richard A
ORCID: Singh, Jarnail
Padgett, Richard A
Venue: Nature Structural & Molecular Biology
Publisher: Springer Science and Business Media LLC
Published: 2009-10-11
Volume: 16
Issue: 11
Pages: 1128-1133
ISSN: 1545-9985 (ISSN-L)
1545-9993
DOI: 10.1038/nsmb.1666
PMC: PMC2783620
OpenAlex: W2074097219
Cited by: 487
References: 47
Citations by year: 2026: 12 · 2025: 16 · 2024: 29 · 2023: 21 · 2022: 29 · 2021: 26 · 2020: 37 · 2019: 25 · 2018: 24 · 2017: 17 · 2016: 32 · 2015: 27 · 2014: 44 · 2013: 38 · 2012: 35
FWCI: 14.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Structural & Molecular Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM079527, R21GM071653)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: transcription rate, RNA polymerase II, pre-mRNA splicing, co-transcriptional splicing, long introns, nuclear RNA processing, intron length
MeSH terms: Dichlororibofuranosylbenzimidazole, Exons, Humans, Introns, Kinetics, RNA Polymerase II, RNA Splicing, RNA, Small Nuclear, Transcription, Genetic, Nucleic Acid Synthesis Inhibitors, Reverse Transcriptase Polymerase Chain Reaction, GTP Phosphohydrolases, Utrophin

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Rates of in situ transcription and splicing in large human genes

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