The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities. Issue 2 (10th September 2013)

• Record Type: Journal Article
• Authors: Molero, Cristina; Petrényi, Katalin; González, Asier; Carmona, Mercè; Gelis, Samuel; Abrie, J. Albert; Strauss, Erick; Ramos, José; Dombradi, Viktor; Hidalgo, Elena; Ariño, Joaquín
• Is Part Of: Molecular microbiology. Volume 90:Issue 2(2013)
• Page Start: 367
• Page End: 382
• Publication Date: 2013-09-10
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12370
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>Saccharomyces cerevisiae</italic> Hal3 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 <italic>Schizosaccharomyces pombe</italic> ORF <italic>SPAC15E1.04</italic> (renamed as <italic>Sp</italic> <italic>hal3</italic>) 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 <italic>Sp</italic> Hal3 and/or its N‐terminal domain retain the ability to bind to and modestly inhibit <italic>in vitro S. cerevisiae</italic> Ppz1 as well as its <italic>S. pombe</italic> homolog Pzh1, and also exhibit PPCDC activity <italic>in vitro</italic> and provide PPCDC function <italic>in vivo</italic>, indicating that <italic>Sp</italic> Hal3 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 <italic>S. cerevisiae</italic> <italic>cdc21</italic> mutant, thus proving TS function. Additionally, we show that the 70 kDa <italic>Sp</italic> Hal3 protein is not proteolytically processed under diverse forms of stress and that, as predicted, <italic>Sp</italic> <italic>hal3</italic> is an essential gene. Therefore, <italic>Sp</italic> <italic>hal3</italic> 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.</p> </abstract>