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2. Formation and nuclear export of ribosomal subunits.

Eukaryotic ribosome formation in the nucleus is a highly dynamic process, which involves the transient interaction of more than 150 non-ribosomal factors with the evolving pre-ribosomal particle in the nucleus. The analysis of the biogenesis and export of ribosomal subunits has been greatly facilitated by the development of the first functional GFP-tagged ribosomal reporters in my laboratory, which allowed us to perform genetic screens for ribosomal export mutants and yielded genes involved not only in export but
also in ribosome biogenesis. By these approaches, we have obtained insights into the complicated mechanism of 60S subunit export, which involves three different types of export receptors. Moreover, we have isolated and ordered pre-ribosomal particles along the path from the nucleolus to the cytoplasm and thus have obtained biochemical “snapshots” of the dynamic nascent 60S and 40S subunits. In addition, we have determined the 3D-EM structure of pre-ribosomal particles (in collaboration with Bettina Böttcher and Meikel Diepholz, EMBL, Heidelberg/Germany). Finally, we could develop in vitro assays to monitor pre-ribosome maturation both by structural and biochemical means. Thus, by applying a variety of interdisciplinary approaches, we could clarify complicated steps of ribosome formation. Future studies involve the mechanistic understanding of the complicated steps during ribosome biogenesis by performing a detailed structure/function analysis of pre-ribosomal particles.


Dieter Kressler, Gert Bange, Yutaka Ogawa, Dagmar Pratte, Bettina Bradatsch, Daniela Roser,
Jun Katahira, Irmgard Sinning, and Ed Hurt:

Coordinated nuclear transport and assembly of functionally related ribosomal proteins onto nascent ribosomes by a common import adaptor
.Science 338, 666-671 (2012)  
 
Sébastien Ferreira-Cerca, Vatsala Sagar, Thorsten Schäfer, Anne-Maria Wesseling, Eileen Chai, Ed Hurt and Nicole LaRonde-LeBlanc:
Structural basis for kinase-activity dependent placeholder role of Rio2 on the evolving pre-40S subunit
.Nat. Struct. Mol. Biol. 19, 1316-1323 (2012)

Jochen Baßler, Isabella Klein, Claudia Schmidt, Emma Thomson, Martina Kallas, Maria Anna Wagner, Gerald Rechberger, Heimo Strohmaier, Ed Hurt, Helmut Bergler:
The conserved Bud20 zinc finger protein is a new component of the ribosomal 60S subunit export machinery
.Mol. Cell Biol. 32, 4898-912 (2012)

Bettina Bradatsch, Christoph Leidig, Sander Granneman, Marén Gnädig, Bettina Böttcher, David Tollervey, Roland Beckman and Ed Hurt:
Structural insight into the late pre-60S ribosomal subunits with bound nuclear export factor Arx1
.Nat. Struct. Mol. Biol. 19, 1234-1241 (2012)

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Jochen Bassler, Martina Kallas, Matthias Thoms, Cornelia Ulbrich, Brigitte Pertschy and Ed Hurt:
The AAA-ATPase Rea1 drives removal of biogenesis factors during multiple stages of 60S ribosome assembly
.Mol. Cell 38, 712-721 (2010)
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Cornelia Ulbrich, Meikel Diepholz, Jochen Baßler, Dieter Kressler, Brigitte Pertschy, Kiki Galani, Bettina Boettcher and Ed Hurt:
Mechanochemical Removal of Ribosome Biogenesis Factors from Nascent 60S Ribosomal Subunits
.Cell 138, 911-9221 (2009)
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Dieter Kressler, Daniela Roser, Brigitte Pertschy and Ed Hurt: The AAA-ATPase Rix7 powers
progression of ribosome biogenesis by stripping Nsa1 from pre-60S particles
.J. Cell Biol. 181, 835-844 (2008).
 
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Bettina Bradatsch, Jun Katahira, Eva Kowalinski, Gert Bange, Wei Yao, Toshihiro Sekimoto,
Viola Baumgärtel, Guido Boese, Jochen Baßler, Klemens Wild, Reiner Peters, Yoshihiro
Yoneda, Irmi Sinning and Ed Hurt:
Arx1 functions as alternative nuclear export receptor
for the 60S pre-ribosomal subunit
.Mol. Cell 27, 767-779 (2007).

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Thorsten Schäfer, Bohumil Maco, Elisabeth Petfalski, David Tollervey, Bettina Boettcher,
Ueli Aebi and Ed Hurt:
A round of phosphorylation/de-phosphorylation triggers maturation of the pre-ribosomal 40S subunit
.Nature 441, 651-655 (2006).

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Tracy A. Nissan, Kyriaki Galani, Bohumil Maco, David Tollervey, Ueli Aebi and Ed Hurt:
A pre-ribosome with a tadpole-like structure functions in ATP-dependent
maturation of 60S subunits
.Mol. Cell 15, 295-301 (2004)


Animation

A ribosomal pre-60S Particle in Motion (movie made by M. Diepholz, EMBL)




1.
Nuclear export of mRNA and its coupling to transcription.


2.
Formation and nuclear export of ribosomes subunits.


3.
Nuclear pore complexes.


4.
Genome and proteome of a thermophilic eukaryote for structural analyses of difficult
proteins and complexes.