title: Protein arginine methylation in Candida albicans: role in nuclear transport.
abstract: Protein arginine methylation plays a key role in numerous eukaryotic processes, such as protein transport and signal transduction. In Candida albicans, two candidate protein arginine methyltransferases (PRMTs) have been identified from the genome sequencing project. Based on sequence comparison, C. albicans candidate PRMTs display similarity to Saccharomyces cerevisiae Hmt1 and Rmt2. Here we demonstrate functional homology of Hmt1 between C. albicans and S. cerevisiae: CaHmt1 supports growth of S. cerevisiae strains that require Hmt1, and CaHmt1 methylates Npl3, a major Hmt1 substrate, in S. cerevisiae. In C. albicans strains lacking CaHmt1, asymmetric dimethylarginine and omega-monomethylarginine levels are significantly decreased, indicating that Hmt1 is the major C. albicans type I PRMT1. Given the known effects of type I PRMTs on nuclear transport of RNA-binding proteins, we tested whether Hmt1 affects nuclear transport of a putative Npl3 ortholog in C. albicans. CaNpl3 allows partial growth of S. cerevisiae npl3Delta strains, but its arginine-glycine-rich C terminus can fully substitute for that of ScNpl3 and also directs methylation-sensitive association with ScNpl3. Expression of green fluorescent protein-tagged CaNpl3 proteins in C. albicans strains with and without CaHmt1 provides evidence for CaHmt1 facilitating export of CaNpl3 in this fungus. We have also identified the C. albicans Rmt2, a type IV fungus- and plant-specific PRMT, by amino acid analysis of an rmt2Delta/rmt2Delta strain, as well as biochemical evidence for additional cryptic PRMTs.
authors.affiliation: Department of Biology, 6500 College Station, Bowdoin College, Brunswick, ME 04011, USA. amcbride@bowdoin.edu
authors.forename: Anne E
authors.initials: AE
authors.lastname: McBride
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zurita-Lopez
authors.forename: Anthony
authors.initials: A
authors.lastname: Regis
authors.forename: Emily
authors.initials: E
authors.lastname: Blum
authors.forename: Ana
authors.initials: A
authors.lastname: Conboy
authors.forename: Shannon
authors.initials: S
authors.lastname: Elf
authors.forename: Steven
authors.initials: S
authors.lastname: Clarke
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism*; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: C077734:NPL3 protein, S cerevisiae; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D001120:Arginine; C475182:HMT1 protein, S cerevisiae; D011484:Protein-Arginine N-Methyltransferases