title: Formation and nuclear export of preribosomes are functionally linked to the small-ubiquitin-related modifier pathway.
abstract: Ribosomal precursor particles are initially assembled in the nucleolus prior to their transfer to the nucleoplasm and export to the cytoplasm. In a screen to identify thermosensitive (ts) mutants defective in the export of pre-60S ribosomal subunit, we isolated the rix16-1 mutant. In this strain, nucleolar accumulation of the Rpl25-eGFP reporter was complemented by UBA2 (a subunit of the E1 sumoylation enzyme). Mutations in UBC9 (E2 enzyme), ULP1 [small-ubiquitin-related modifier (SUMO) isopeptidase] and SMT3 (SUMO-1) caused 60S export defects. A directed analysis of the SUMO proteome revealed that many ribosome biogenesis factors are sumoylated. Importantly, preribosomal particles along both the 60S and the 40S synthesis pathways were decorated with SUMO, showing its direct involvement. Consistent with this, early 60S assembly factors were genetically linked to SUMO conjugation. Notably, the SUMO deconjugating enzyme Ulp1, which localizes to the nuclear pore complex (NPC), was functionally linked to the 60S export factor Mtr2. Together our data suggest that sumoylation of preribosomal particles in the nucleus and subsequent desumoylation at the NPC is necessary for efficient ribosome biogenesis and export in eukaryotes.
authors.affiliation: Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
authors.forename: Vikram Govind
authors.initials: VG
authors.lastname: Panse
authors.forename: Dieter
authors.initials: D
authors.lastname: Kressler
authors.forename: Andrea
authors.initials: A
authors.lastname: Pauli
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petfalski
authors.forename: Marén
authors.initials: M
authors.lastname: Gnädig
authors.forename: David
authors.initials: D
authors.lastname: Tollervey
authors.forename: Ed
authors.initials: E
authors.lastname: Hurt
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011498:Protein Precursors / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D011498:Protein Precursors; D021122:Protein Subunits; D012322:RNA Precursors; D012335:RNA, Ribosomal; D011993:Recombinant Fusion Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D003546:Cysteine Endopeptidases; C118083:Ulp1 protease