title: Two functionally distinct domains generated by in vivo cleavage of Nup145p: a novel biogenesis pathway for nucleoporins.
abstract: Nup145p is an essential yeast nucleoporin involved in nuclear export of polyadenylated RNAs. We demonstrate here that Nup145p is cleaved in vivo to yield two functionally distinct domains: a carboxy-terminal domain (C-Nup145p) which is located at the nuclear pore complex (NPC) and assembles into the Nup84p complex, and a GLFG-containing amino-terminal domain (N-Nup145p) which is not part of this complex. Whereas the essential C-Nup145p accomplishes the functions required for efficient mRNA export and normal NPC distribution, N-Nup145p, which is homologous to the GLFG-containing nucleoporins Nup100p and Nup116p, is not necessary for cell growth. However, the N-Nup145p becomes essential in a nup188 mutant background. Strikingly, generation of a free N-domain is a prerequisite for complementation of this peculiar synthetic lethal mutant. These data suggest that N- and C-domains of Nup145p perform independent functions, and that the in vivo cleavage observed is of functional importance.
authors.affiliation: Unité de Génétique Moléculaire des levures (URA 1300 CNRS and UPR 927 Univ. P M Curie), Institut Pasteur, Département des Biotechnologies, Paris, France.
authors.forename: M T
authors.initials: MT
authors.lastname: Teixeira
authors.forename: S
authors.initials: S
authors.lastname: Siniossoglou
authors.forename: S
authors.initials: S
authors.lastname: Podtelejnikov
authors.forename: J C
authors.initials: JC
authors.lastname: Bénichou
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: B
authors.initials: B
authors.lastname: Dujon
authors.forename: E
authors.initials: E
authors.lastname: Hurt
authors.forename: E
authors.initials: E
authors.lastname: Fabre
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009685:Nuclear Envelope / Q000737:chemistry* / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013205:Staphylococcal Protein A / Q000235:genetics; D015003:Yeasts / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; C088627:NUP145 protein, S cerevisiae; C097894:NUP84 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D013205:Staphylococcal Protein A