RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae

  1. Eduardo Eyras1,4,6
  1. 1Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
  2. 2Molecular Biology Institute of Barcelona (IBMB), 08028 Barcelona, Spain
  3. 3Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain
  4. 4Catalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
    • 5 Present address: The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.

    Abstract

    Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 3′ splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 3′ss in the CDS and 5′ UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 3′ss. Experimental validation of a number of predicted alternative 3′ss shows that their usage is low compared to annotated 3′ss. The majority of these alternative 3′ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 3′ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression.

    Keywords

    Footnotes

    • Received October 5, 2011.
    • Accepted March 8, 2012.

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