The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities

Cristina Molero, Katalin Petrényi, Asier González, Mercè Carmona, Samuel Gelis, J. Albert Abrie, Erick Strauss, José Ramos, Viktor Dombradi, Elena Hidalgo, Joaquín Ariño

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Summary: Saccharomyces cerevisiaeHal3 and Vhs3 are moonlighting proteins, forming an atypical heterotrimeric decarboxylase (PPCDC) required for CoA biosynthesis, and regulating cation homeostasis by inhibition of the Ppz1 phosphatase. The Schizosaccharomyces pombeORF SPAC15E1.04 (renamed as Sphal3) encodes a protein whose amino-terminal half is similar to Sc Hal3 whereas its carboxyl-terminal half is related to thymidylate synthase (TS). We show that SpHal3 and/or its N-terminal domain retain the ability to bind to and modestly inhibit in vitro S.cerevisiaePpz1 as well as its S.pombe homolog Pzh1, and also exhibit PPCDC activity in vitro and provide PPCDC function in vivo, indicating that SpHal3 is a monogenic PPCDC in fission yeast. Whereas the Sp Hal3 N-terminal domain partially mimics Sc Hal3 functions, the entire protein and its carboxyl-terminal domain rescue the S.cerevisiaecdc21 mutant, thus proving TS function. Additionally, we show that the 70kDa Sp Hal3 protein is not proteolytically processed under diverse forms of stress and that, as predicted, Sphal3 is an essential gene. Therefore, Sphal3 represents a fusion event that joined three different functional activities in the same gene. The possible advantage derived from this surprising combination of essential proteins is discussed.

Original languageEnglish
Pages (from-to)367-382
Number of pages16
JournalMolecular Microbiology
Volume90
Issue number2
DOIs
Publication statusPublished - Oct 1 2013

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Molero, C., Petrényi, K., González, A., Carmona, M., Gelis, S., Abrie, J. A., Strauss, E., Ramos, J., Dombradi, V., Hidalgo, E., & Ariño, J. (2013). The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities. Molecular Microbiology, 90(2), 367-382. https://doi.org/10.1111/mmi.12370