Transcription rate strongly affects splicing fidelity and cotranscriptionality in budding yeast

  1. Jean D. Beggs1
  1. 1Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom;
  2. 2School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, United Kingdom
  • 3 Present address: MRC Human Genomics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK

  • 4 Present address: European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD, UK

  • Corresponding author: jbeggs{at}ed.ac.uk
  • Abstract

    The functional consequences of alternative splicing on altering the transcription rate have been the subject of intensive study in mammalian cells but less is known about effects of splicing on changing the transcription rate in yeast. We present several lines of evidence showing that slow RNA polymerase II elongation increases both cotranscriptional splicing and splicing efficiency and that faster elongation reduces cotranscriptional splicing and splicing efficiency in budding yeast, suggesting that splicing is more efficient when cotranscriptional. Moreover, we demonstrate that altering the RNA polymerase II elongation rate in either direction compromises splicing fidelity, and we reveal that splicing fidelity depends largely on intron length together with secondary structure and splice site score. These effects are notably stronger for the highly expressed ribosomal protein coding transcripts. We propose that transcription by RNA polymerase II is tuned to optimize the efficiency and accuracy of ribosomal protein gene expression, while allowing flexibility in splice site choice with the nonribosomal protein transcripts.

    Footnotes

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.225615.117.

    • Freely available online through the Genome Research Open Access option.

    • Received May 25, 2017.
    • Accepted December 14, 2017.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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