title: Internal initiation drives the synthesis of Ure2 protein lacking the prion domain and affects [URE3] propagation in yeast cells.
abstract: The [URE3] phenotype in Saccharomyces cerevisiae is caused by the inactive, altered (prion) form of the Ure2 protein (Ure2p), a regulator of nitrogen catabolism. Ure2p has two functional domains: an N-terminal domain necessary and sufficient for prion propagation and a C-terminal domain responsible for nitrogen regulation. We show here that the mRNA encoding Ure2p possesses an IRES (internal ribosome entry site). Internal initiation leads to the synthesis of an N-terminally truncated active form of the protein (amino acids 94-354) lacking the prion-forming domain. Expression of the truncated Ure2p form (94-354) mediated by the IRES element cures yeast cells of the [URE3] phenotype. We assume that the balance between the full-length and truncated (94-354) Ure2p forms plays an important role in yeast cell physiology and differentiation.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Bern, Buehlstrasse 28, 3012 Bern, Switzerland. aak11@po.cwru.edu
authors.forename: Anton A
authors.initials: AA
authors.lastname: Komar
authors.forename: Thierry
authors.initials: T
authors.lastname: Lesnik
authors.forename: Christophe
authors.initials: C
authors.lastname: Cullin
authors.forename: William C
authors.initials: WC
authors.lastname: Merrick
authors.forename: Hans
authors.initials: H
authors.lastname: Trachsel
authors.forename: Michael
authors.initials: M
authors.lastname: Altmann
mesh_terms: D000818:Animals; D048429:Cell Size; D018387:Codon, Initiator; D017930:Genes, Reporter; D005979:Glutathione Peroxidase; D010442:Peptide Chain Initiation, Translational; D010641:Phenotype; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020506:Untranslated Regions
chemical_list: D018387:Codon, Initiator; D011328:Prions; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D020506:Untranslated Regions; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae