title: The functions of Mediator in Candida albicans support a role in shaping species-specific gene expression.
abstract: The Mediator complex is an essential co-regulator of RNA polymerase II that is conserved throughout eukaryotes. Here we present the first study of Mediator in the pathogenic fungus Candida albicans. We focused on the Middle domain subunit Med31, the Head domain subunit Med20, and Srb9/Med13 from the Kinase domain. The C. albicans Mediator shares some roles with model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, such as functions in the response to certain stresses and the role of Med31 in the expression of genes regulated by the activator Ace2. The C. albicans Mediator also has additional roles in the transcription of genes associated with virulence, for example genes related to morphogenesis and gene families enriched in pathogens, such as the ALS adhesins. Consistently, Med31, Med20, and Srb9/Med13 contribute to key virulence attributes of C. albicans, filamentation, and biofilm formation; and ALS1 is a biologically relevant target of Med31 for development of biofilms. Furthermore, Med31 affects virulence of C. albicans in the worm infection model. We present evidence that the roles of Med31 and Srb9/Med13 in the expression of the genes encoding cell wall adhesins are different between S. cerevisiae and C. albicans: they are repressors of the FLO genes in S. cerevisiae and are activators of the ALS genes in C. albicans. This suggests that Mediator subunits regulate adhesion in a distinct manner between these two distantly related fungal species.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Uwamahoro
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.forename: Branka
authors.initials: B
authors.lastname: Jelicic
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Lo
authors.forename: Cecile
authors.initials: C
authors.lastname: Beaurepaire
authors.forename: Farkad
authors.initials: F
authors.lastname: Bantun
authors.forename: Tara
authors.initials: T
authors.lastname: Quenault
authors.forename: Peter R
authors.initials: PR
authors.lastname: Boag
authors.forename: Georg
authors.initials: G
authors.lastname: Ramm
authors.forename: Judy
authors.initials: J
authors.lastname: Callaghan
authors.forename: Traude H
authors.initials: TH
authors.lastname: Beilharz
authors.forename: André
authors.initials: A
authors.lastname: Nantel
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
mesh_terms: D018441:Biofilms / Q000254:growth & development; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D013045:Species Specificity; D014774:Virulence / Q000235:genetics
chemical_list: C093538:ALS1 protein, Candida albicans; D005656:Fungal Proteins; D056892:Mediator Complex; C492627:SOH1 protein, S cerevisiae; C074748:SRB2 protein, S cerevisiae; C093967:SSN2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins