Nascent Transcript Folding Plays a Major Role in Determining RNA Polymerase Elongation Rates
| Autor: | Benjamin D. Goddard, Aleksandra Helwak, Elisabeth Petfalski, Tomasz W. Turowski, David Tollervey, Sarah L. French |
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| Rok vydání: | 2020 |
| Předmět: |
RNA Folding
Transcription Elongation Genetic RNA Splicing rDNA Saccharomyces cerevisiae yeast Biology DNA Ribosomal Article 03 medical and health sciences chemistry.chemical_compound cotranscriptional events 0302 clinical medicine RNA Polymerase I Transcription (biology) Gene Expression Regulation Fungal RNA polymerase Schizosaccharomyces RNA polymerase I nascent RNA transcription elongation Molecular Biology Polymerase 030304 developmental biology Transcription bubble Base Composition RNA polymerase 1 0303 health sciences Binding Sites Base Sequence mathematical modeling RNA Polymerase III RNA RNA Fungal Cell Biology Chromatin DNA topology Cell biology RNA processing chemistry RNA splicing biology.protein Thermodynamics RNA Polymerase II RNA Splice Sites Elongation 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Molecular Cell Turowski, T, Petfalski, E, Goddard, B D, French, S L, Helwak, A & Tollervey, D 2020, ' Nascent transcript folding plays a major role in determining RNA polymerase elongation rates ', Molecular Cell, vol. 79, no. 3, pp. 488-503.e11 . https://doi.org/10.1016/j.molcel.2020.06.002 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2020.06.002 |
| Popis: | Summary Transcription elongation rates influence RNA processing, but sequence-specific regulation is poorly understood. We addressed this in vivo, analyzing RNAPI in S. cerevisiae. Mapping RNAPI by Miller chromatin spreads or UV crosslinking revealed 5′ enrichment and strikingly uneven local polymerase occupancy along the rDNA, indicating substantial variation in transcription speed. Two features of the nascent transcript correlated with RNAPI distribution: folding energy and GC content in the transcription bubble. In vitro experiments confirmed that strong RNA structures close to the polymerase promote forward translocation and limit backtracking, whereas high GC in the transcription bubble slows elongation. A mathematical model for RNAPI elongation 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 use, indicating regulatory significance for transcript folding. Graphical Abstract 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 Transcription elongation is a stochastic process that can go backward as well as forward. Here Turowski et al. report that folding of the nascent transcript immediately behind the polymerase resists backtracking and promotes forward movement. This results in faster elongation relative to unstructured sequences and is potentially important for cotranscriptional processing. |
| Databáze: | OpenAIRE |
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