title: A RanGTP-independent mechanism allows ribosomal protein nuclear import for ribosome assembly.
abstract: Within a single generation time a growing yeast cell imports ∼14 million ribosomal proteins (r-proteins) into the nucleus for ribosome production. After import, it is unclear how these intrinsically unstable and aggregation-prone proteins are targeted to the ribosome assembly site in the nucleolus. Here, we report the discovery of a conserved nuclear carrier Tsr2 that coordinates transfer of the r-protein eS26 to the earliest assembling pre-ribosome, the 90S. In vitro studies revealed that Tsr2 efficiently dissociates importin:eS26 complexes via an atypical RanGTP-independent mechanism that terminates the import process. Subsequently, Tsr2 binds the released eS26, shields it from proteolysis, and ensures its safe delivery to the 90S pre-ribosome. We anticipate similar carriers-termed here escortins-to securely connect the nuclear import machinery with pathways that deposit r-proteins onto developing pre-ribosomal particles.
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland Molecular Life Science Graduate School, University of Zurich, Zurich, Switzerland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Schütz
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Ute
authors.initials: U
authors.lastname: Fischer
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland Molecular Life Science Graduate School, University of Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Altvater
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland Molecular Life Science Graduate School, University of Zurich, Zurich, Switzerland.
authors.forename: Purnima
authors.initials: P
authors.lastname: Nerurkar
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Cohue
authors.initials: C
authors.lastname: Peña
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Michaela
authors.initials: M
authors.lastname: Gerber
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, Universität des Saarlandes, Homburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Caesar
authors.affiliation: Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland Systems Biology Graduate School, Zurich, Zurich, Switzerland.
authors.forename: Olga T
authors.initials: OT
authors.lastname: Schubert
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, Universität des Saarlandes, Homburg, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schlenstedt
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland vikram.panse@bc.biol.ethz.ch.
authors.forename: Vikram G
authors.initials: VG
authors.lastname: Panse
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D028884:Karyopherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D012337:RNA, Ribosomal, 18S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C101820:KAP104 protein, S cerevisiae; C109173:Kap123 protein, S cerevisiae; D028884:Karyopherins; D012337:RNA, Ribosomal, 18S; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D028961:beta Karyopherins
keywords: Diamond-Blackfan anemia (DBA); Tsr2; eS26; nuclear import; rRNA processing; ribosome biogenesis