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Promoter-driven splicing regulation in fission yeast

Nature volume 455, pages 997–1000 (2008)Cite this article

Abstract

The meiotic cell cycle is modified from the mitotic cell cycle by having a pre-meiotic S phase that leads to high levels of recombination, two rounds of nuclear division with no intervening DNA synthesis and a reductional pattern of chromosome segregation. Rem1 is a cyclin that is only expressed during meiosis in the fission yeast Schizosaccharomyces pombe. Cells in which rem1 has been deleted show decreased intragenic meiotic recombination and a delay at the onset of meiosis I (ref. 1). When ectopically expressed in mitotically growing cells, Rem1 induces a G1 arrest followed by severe mitotic catastrophes. Here we show that rem1 expression is regulated at the level of both transcription and splicing, encoding two proteins with different functions depending on the intron retention. We have determined that the regulation of rem1 splicing is not dependent on any transcribed region of the gene. Furthermore, when the rem1 promoter is fused to other intron-containing genes, the chimaeras show a meiotic-specific regulation of splicing, exactly the same as endogenous rem1. This regulation is dependent on two transcription factors of the forkhead family, Mei4 (ref. 2) and Fkh2 (ref. 3). Whereas Mei4 induces both transcription and splicing of rem1, Fkh2 is responsible for the intron retention of the transcript during vegetative growth and the pre-meiotic S phase.

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Figure 1: Alternatively spliced rem1 restores normal recombination levels.
Figure 2: The promoter of rem1 controls splicing.
Figure 3: rem1 splicing is dependent on forkhead transcription factors.
Figure 4: Mei4 loads the spliceosome onto rem1.

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ArrayExpress

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Microarray data are available at ArrayExpress (www.ebi.ac.uk/arrayexpress/) under the accession number E-TABM-465.

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Acknowledgements

We thank P. Nurse, K. Gould, C. Query, N. Kaufer, H. Murakami and C. McInerny for strains and plasmids; J. Wu and Y. Zhurinskiy for help and advice on ChIPs; E. Hidalgo, J. Valcárcel, J. Vilardell and G. Gil for critical reading of the manuscript; and members of the Oxidative Stress and Cell Cycle Group at Universitat Pompeu Fabra and P. Nurse’s laboratory at Rockefeller University for suggestions and comments. We acknowledge the technical support of M. Carmona and K. Zueckert-Gaudenz. J.A. is supported by a contract Ramon y Cajal from the Ministerio de Educación y Ciencia. This work was supported by grants from the Ministerio de Ciencia y Tecnologia (BFU2006-01785) and the Consolider-Ingenio 2007-0020.

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Authors and Affiliations

  1. Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/Doctor Aiguader 88, Barcelona 08003, Spain ,

    Alberto Moldón, Jordi Malapeira, Natalia Gabrielli, Blanca Gómez-Escoda, Tsvetomira Ivanova & José Ayté

  2. Stowers Institute, Kansas City, Missouri 64110, USA ,

    Madelaine Gogol & Chris Seidel

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  1. Alberto Moldón
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Correspondence to José Ayté.

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Moldón, A., Malapeira, J., Gabrielli, N. et al. Promoter-driven splicing regulation in fission yeast. Nature 455, 997–1000 (2008). https://doi.org/10.1038/nature07325

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