Cited by 75Genomics and Chromatin DynamicsRNA Research and SplicingRNA and protein synthesis mechanisms

Nascent Transcript Folding Plays a Major Role in Determining RNA Polymerase Elongation Rates

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Turowski, Tomasz W., Petfalski, Elisabeth, Goddard, Benjamin D., French, Sarah L., Helwak, Aleksandra, Tollervey, David·2020·Molecular Cell

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Abstract

ABSTRACT Transcription elongation rates are important for RNA processing, but sequence-specific regulation is poorly understood. We addressed this in vivo , analyzing RNAPI in S.cerevisiae . Analysis of Miller chromatin spreads and mapping RNAPI using UV crosslinking, revealed a marked 5’ bias and strikingly uneven local polymerase occupancy, indicating substantial variation in transcription speed. Two features of the nascent transcript correlated with RNAPI distribution; folding energy and G+C-content. In vitro experiments confirmed that strong RNA structures close to the polymerase promote forward translocation and limit backtracking, whereas high G+C within the transcription bubble slows elongation. We developed a mathematical model for RNAPI elongation, which confirmed the importance of nascent RNA folding in transcription. RNAPI from S.pombe was similarly sensitive to transcript folding, as were S.cerevisiae RNAPII and RNAPIII. For RNAPII, unstructured RNA, which favors slowed elongation, was associated with faster cotranscriptional splicing and proximal splice site usage indicating regulatory significance for transcript folding. Abstract Figure HIGHLIGHTS Structures in the nascent RNA correlate with rapid elongation by RNAPI in vivo Stable RNA structures limit RNAPI backtracking in vitro GC content in the transcription bubble tunes transcription elongation rate Nascent transcript folding modulates dynamics of all three RNAPs in vivo

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Crossref · 10.1016/j.molcel.2020.06.002

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  • In vivo experiments in budding yeast showed that fast transcription elongation by RNA Pol II is associated with strong nascent RNA structures which would prevent RNA Pol II from backtracking thus pushing it forward.

    “Along the same line, in vivo experiments in budding yeast showed that fast transcription elongation by RNA Pol II is associated with strong nascent RNA structures which would prevent RNA Pol II from backtracking thus pushing it forward (Turowski et al, 2020).”

    From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Turowski et al, 2020

    The Results section, “Effects of RNA Folding Are Widespread and Have Regulatory Potential” (page unavailable), reports that RNAPII occupancy troughs in budding yeast, interpreted as rapid elongation, were associated with stronger nascent RNA structures. But the experiments showing that strong structures limit backtracking and promote forward translocation were performed in vitro with RNAPI, not demonstrated for RNAPII in vivo. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • High GC content in the transcription bubble slows down RNA polymerase I transcription, while strong nascent RNA structures formed close to the polymerase promote forward movement.

    “For example, while high GC content in the transcription bubble slows down RNA polymerase I transcription, strong nascent RNA structures formed close to the polymerase promote forward movement (Turowski et al, 2020).”

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Authors
Turowski, T. W., Petfalski, E., Goddard, B. D., French, S. L., Helwak, A., & Tollervey, D.
Affiliations
  • Wellcome Centre for Cell Biology (GB)
  • Maxwell Institute for Mathematical Sciences (GB)
  • University of Virginia (US)
Corresponding author
  • Turowski, Tomasz W.
  • Tollervey, David
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2020-08
Volume
79
Issue
3
Pages
488-503.e11
ISSN
1097-2765 (ISSN-L)
OpenAlex
W3037785698
Cited by
75
References
100
Citations by year
2026: 8 · 2025: 10 · 2024: 11 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 3
FWCI
3.65
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
Wellcome Trust
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 › RNA and protein synthesis mechanisms
Keywords
transcription elongation, RNA secondary structure, GC content, transcription bubble, RNA polymerase I, RNA polymerase II, RNA polymerase III, Saccharomyces cerevisiae, Schizosaccharomyces pombe, ribosomal DNA, co-transcriptional splicing
MeSH terms
Base Composition, Base Sequence, Binding Sites, Chromatin, DNA, Ribosomal, Protein Binding, RNA Polymerase I, RNA Polymerase II, RNA Polymerase III, RNA Splicing, RNA, Fungal, Saccharomyces cerevisiae, Schizosaccharomyces, Thermodynamics, Gene Expression Regulation, Fungal, RNA Splice Sites, RNA Folding, Transcription Elongation, Genetic

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