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Exploring the interface between ribosome assembly and nucleocytoplasmic transport

English title Exploring the interface between ribosome assembly and nucleocytoplasmic transport
Applicant Panse Vikram
Number 166571
Funding scheme Project funding (Div. I-III)
Research institution Institut für Medizinische Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Biochemistry
Start/End 01.10.2016 - 31.07.2020
Approved amount 678'000.00
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All Disciplines (2)

Discipline
Biochemistry
Molecular Biology

Keywords (4)

ribosome assembly; nuclear import; nuclear transport; RanGTP, Crm1, Slx9

Lay Summary (German)

Lead
Erforschung der Schnittstelle zwischen Kern-Zellplasma Transport und Ribosom Montage
Lay summary
Die fehlerfreie Übersetzung des genetischen Codes in Proteine ist der Schlüssel für Zellwachstum und Proliferation. Diese wesentliche Aufgabe wird durch das Ribosom durchgeführt. Während die Struktur des fertigen Ribosoms uns Einblicke in  den Molekularen Mechanismen der Translation gibt, ist unser Wissen in Bezug auf die Montage, Qualitätskontrolle und das zelluläre Targeting dieser Universalmaschine  erst im Entstehen. Die Assemblierung eukaryotischer Ribosomen  ist ein spektakuläres Beispiel für einen hochdynamischen Prozess, der sich über verschiedene zelluläre Gebiete erstreckt: dem Nukleolus, dem Nukleoplasma und dem Zytoplasma. Dieser Prozess, der im Nukleolus beginnt, erfordert > 300 konservierte, transient assoziierende Assemblierungsproteine, deren Wirkungsort(e) und –funktion(en) während der Assemblierung nur langsam aufgeklärt werden. Die Assemblierung eukaryotischer Ribosomen stützt sich auch auf einen effizienten Transport zwischen Nukleus und Zytoplasma. Im Modellorganismus Bäckerhefe liefert die Importmaschinerie  ~ 140.000 ribosomale Proteine jede Minute in den Kern, um in die Ribosomen eingebaut zu werden. Innerhalb der gleichen Zeit ermöglicht die Exportmaschinerie die Translokation von ~ 2000 prä-ribosomalen Partikel jede Minute durch ~ 200 Kernporenkomplexe in das Zytoplasma. Durch Nutzung des Organismus Bäckerhefe versuchen wir 2 Mechanismen zu entschlüsseln:
 
(1) Den Mechanismus, mit denen ribosomale Proteine gezielt an ihren rRNA-Bindungsstelle  in prä-ribosomale Partikel in der Kernkörperchen  eingebaut werden
(2) Die Mechanismen, durch die prä-ribosomalen Partikel für den Transport durch Kernporenkomplexe vorbereitet werden
 
Unsere Analysen werden Aufschluss darüber geben, wie die Transportmaschinen die prä-Ribosomen vom Nukleus zum Zytoplasma transportieren und wie die Assemblierung der Ribosomen und die Qualitätskontrolle zusammenarbeiten, um funktionelle Ribosomen für die Translation herzustellen.

Direct link to Lay Summary Last update: 09.08.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
The ribotoxin α-sarcin can cleave the sarcin/ricin loop on late 60S pre-ribosomes
Olombrada Miriam, Peña Cohue, Rodríguez-Galán Olga, Klingauf-Nerurkar Purnima, Portugal-Calisto Daniela, Oborská-Oplová Michaela, Altvater Martin, Gavilanes José G, Martínez-del-Pozo Álvaro, de la Cruz Jesús, García-Ortega Lucía, Panse Vikram Govind (2020), The ribotoxin α-sarcin can cleave the sarcin/ricin loop on late 60S pre-ribosomes, in Nucleic Acids Research, 48(11), 6210-6222.
Divergent Evolution of Legionella RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
Swart A. Leoni, Steiner Bernhard, Gomez-Valero Laura, Schütz Sabina, Hannemann Mandy, Janning Petra, Irminger Michael, Rothmeier Eva, Buchrieser Carmen, Itzen Aymelt, Panse Vikram Govind, Hilbi Hubert (2020), Divergent Evolution of Legionella RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets, in mBio, 11(2), 1-14.
The GTPase Nog1 co-ordinates the assembly, maturation and quality control of distant ribosomal functional centers
Klingauf-Nerurkar Purnima, Gillet Ludovic C, Portugal-Calisto Daniela, Oborská-Oplová Michaela, Jäger Martin, Schubert Olga T, Pisano Agnese, Peña Cohue, Rao Sanjana, Altvater Martin, Chang Yiming, Aebersold Ruedi, Panse Vikram G (2020), The GTPase Nog1 co-ordinates the assembly, maturation and quality control of distant ribosomal functional centers, in eLife, 9, 1-25.
Conserved phosphorylation hotspots in eukaryotic protein domain families
Strumillo Marta J., Oplová Michaela, Viéitez Cristina, Ochoa David, Shahraz Mohammed, Busby Bede P., Sopko Richelle, Studer Romain A., Perrimon Norbert, Panse Vikram G., Beltrao Pedro (2019), Conserved phosphorylation hotspots in eukaryotic protein domain families, in Nature Communications, 10(1), 1977-1977.
Co-translational assembly of proteasome subunits in NOT1-containing assemblysomes
Panasenko Olesya O., Somasekharan Syam Prakash, Villanyi Zoltan, Zagatti Marina, Bezrukov Fedor, Rashpa Ravish, Cornut Julien, Iqbal Jawad, Longis Marion, Carl Sarah H., Peña Cohue, Panse Vikram G., Collart Martine A. (2019), Co-translational assembly of proteasome subunits in NOT1-containing assemblysomes, in Nature Structural & Molecular Biology, 26(2), 110-120.
Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2
Schütz Sabina, Michel Erich, Damberger Fred F., Oplová Michaela, Peña Cohue, Leitner Alexander, Aebersold Ruedi, Allain Frederic H.-T., Panse Vikram Govind (2018), Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2, in Nature Communications, 9(1), 3669-3669.
Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis
Khajuria Rajiv K., Munschauer Mathias, Ulirsch Jacob C., Fiorini Claudia, Ludwig Leif S., McFarland Sean K., Abdulhay Nour J., Specht Harrison, Keshishian Hasmik, Mani D.R., Jovanovic Marko, Ellis Steven R., Fulco Charles P., Engreitz Jesse M., Schütz Sabina, Lian John, Gripp Karen W., Weinberg Olga K., Pinkus Geraldine S., Gehrke Lee, Regev Aviv, Lander Eric S., Gazda Hanna T., Lee Winston Y., et al. (2018), Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis, in Cell, 173(1), 90-103.e19.
Structure of a eukaryotic cytoplasmic pre‐40S ribosomal subunit
Scaiola Alain, Peña Cohue, Weisser Melanie, Böhringer Daniel, Leibundgut Marc, Klingauf‐Nerurkar Purnima, Gerhardy Stefan, Panse Vikram Govind, Ban Nenad (2018), Structure of a eukaryotic cytoplasmic pre‐40S ribosomal subunit, in The EMBO Journal, 37(7), 1-10.
Eukaryotic ribosome assembly, transport and quality control
Peña Cohue, Hurt Ed, Panse Vikram Govind (2017), Eukaryotic ribosome assembly, transport and quality control, in Nature Structural & Molecular Biology, 24(9), 689-699.
Prefabrication of a ribosomal protein subcomplex essential for eukaryotic ribosome formation
Peña Cohue, Schütz Sabina, Fischer Ute, Chang Yiming, Panse Vikram G (2016), Prefabrication of a ribosomal protein subcomplex essential for eukaryotic ribosome formation, in eLife, 5, 1-24.

Collaboration

Group / person Country
Types of collaboration
Prof. Nenad Ban ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Hubert Hilbi UZH Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Roland Sigel UZH Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Martine Collart University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. Ruedi Aebersold ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Pedro Beltrao EMBL Hinxton Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Fred Allain ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EMBO Ribosome Synthesis Meeting Talk given at a conference Role of Puf6 during early ribosome formation 09.08.2018 Orford, Canada Panse Vikram;
EMBO Ribosome Synthesis Meeting Poster Cytoplasmic maturation of the 40S pre-ribosome 09.08.2018 Orford, Canada, Canada Peña Chou Cohue; Klingauf-Nerurkar Purnima; Oplová Michaela; Panse Vikram; Schütz Sabina Claudia;
EMBO Ribosome Synthesis Meeting Poster Pre-fabrication of a ribosomal protein complex essential for ribosome formation 09.08.2018 Orford, Canada Schütz Sabina Claudia; Klingauf-Nerurkar Purnima; Peña Chou Cohue; Panse Vikram; Oplová Michaela;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Laudinella Stiftung School Camps Rhaeto-Romanic Switzerland German-speaking Switzerland 2019

Awards

Title Year
ETH Silver Medal for thesis work submitted by Dr. Cohue Pena 2018

Associated projects

Number Title Start Funding scheme
188527 Orchestrating eukaryotic ribosome assembly with flexible/disordered protein tails 01.08.2020 Project funding (Div. I-III)
152995 Exploring the interface between ribosome assembly and nucleo-cytoplasmic transport 01.08.2014 SNSF Professorships
170811 Enhanced Resolution Confocal Laser Scanning Microscope 01.10.2017 R'EQUIP
183382 A state-of-the-art detector for cryo-electron microscopy 01.06.2019 R'EQUIP

Abstract

Error-free translation of the genetic code to proteins is key to cellular growth and proliferation. This essential task is carried out by the ribosome. While the structure of the mature ribosome is giving insights into the mechanics of translation, our knowledge regarding the assembly, quality control and cellular targeting of this universal machine is emerging. Eukaryotic ribosome assembly is a spectacular example of a highly dynamic and regulated process that stretches across different cellular territories: the nucleolus, nucleoplasm and the cytoplasm. This poorly understood process, which begins in the nucleolus, requires >300 conserved transiently associating assembly factors, whose site(s) of action and function(s) on maturing pre-ribosomal particles are beginning to be elucidated. Eukaryotic ribosome assembly also relies on efficient nucleocytoplasmic transport. In the model organism budding yeast, the import machinery delivers ~140,000 ribosomal proteins every minute to the nucleus for ribosome assembly. Within the same time, the export machinery facilitates translocation of ~2000 pre-ribosomal particles every minute through ~200 nuclear pore complexes into the cytoplasm. By exploiting the genetically tractable organism budding yeast, in combination with biochemical and structural biology approaches, we will uncover:(1) Mechanisms by which ribosomal proteins are precisely targeted to their rRNA binding site on assembling pre-ribosomal particles in the nucleolus. (2) Mechanisms by which pre-ribosomal particles are prepared for transport through nuclear pore complexes. Our analyses will shed light on how the nucleocytoplasmic transport machinery, the ribosome assembly pathway and the quality control machinery co-ordinate their activities to commit functional ribosomes for translation.
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