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  • The EMBO Journal (2008) 27, 2411 - 2421
  • doi:10.1038/emboj.2008.165

Published online: 21 August 2008

Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate biosynthetic pathwaysEMBO Open

Marta Kwapisz1,2,a, Maxime Wery1,a, Daphné Després1, Yad Ghavi-Helm1, Julie Soutourina1, Pierre Thuriaux1 and François Lacroute2,3

  1. CEA, iBiTec-S, Service de Biologie Intégrative et Génétique Moléculaire, Gif-sur-Yvette, France
  2. CNRS, Centre de Génétique Moléculaire, UPR2167, Gif-sur-Yvette, France
  3. Université Pierre et Marie Curie, Paris, France

Correspondence to:

Pierre Thuriaux, CEA, iBiTec-S, Service de Biologie Intégrative et Génétique Moléculaire, Gif sur Yvette F-91191, France. Tel.: +33 1 69 08 35 86; Fax: +33 1 69 08 47 12; E-mail: pierre.thuriaux@cea.fr

aThese authors contributed equally to this work

Received 2 June 2008; Accepted 30 July 2008

The yeast URA2 gene, encoding the rate-limiting enzyme of UTP biosynthesis, is transcriptionally activated by UTP shortage. In contrast to other genes of the UTP pathway, this activation is not governed by the Ppr1 activator. Moreover, it is not due to an increased recruitment of RNA polymerase II at the URA2 promoter, but to its much more effective progression beyond the URA2 mRNA start site(s). Regulatory mutants constitutively expressing URA2 resulted from cis-acting deletions upstream of the transcription initiator region, or from amino-acid replacements altering the RNA polymerase II Switch 1 loop domain, such as rpb1-L1397S. These two mutation classes allowed RNA polymerase to progress downstream of the URA2 mRNA start site(s). rpb1-L1397S had similar effects on IMD2 (IMP dehydrogenase) and URA8 (CTP synthase), and thus specifically activated the rate-limiting steps of UTP, GTP and CTP biosynthesis. These data suggest that the Switch 1 loop of RNA polymerase II, located at the downstream end of the transcription bubble, may operate as a specific sensor of the nucleoside triphosphates available for transcription.

  • Keywords:

    • IMD2,
    • IMD3,
    • S. cerevisiae,
    • URA2,
    • URA8

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