Formation, maturation and nuclear export of pre-ribosomal subunits
Final Report Abstract
During the last grant period we were able to characterize the functional aspects of the nuclear maturation of the peptidyl transferase center (PTC) and the central protuberance (CP) of the large ribosomal subunit. Both structural features are essential for the function of the 60S ribosomal subunit during translation. Remarkably, the huge Rea1 ATPase is involved in both maturation events. Its ATPase ring domain attaches together with the Rix1 subcomplex at the nascent central protuberance, which triggers the rotation of the 5S RNP towards into its mature position. By using its MIDAS domain, which is attached to a long linker domain, Rea1 contacts Rsa4 that is positioned between the nascent central protuberance and the peptidyl transferase center. Our results revealed that Rea1 mediated ATP hydrolysis induces the release of Rsa4, which is connected by Nsa2 with the immature PTC. Thus, we concluded that the active removal of Rsa4 is important to initiate the structural rearrangement of immature PTC. Moreover, the release of Rsa4 appears to activate the release of the GTPase Nug2, which in turn is a prerequisite for the subsequent recruitment of export factors. In summary, a sophisticated network of biogenesis factors around Rea1 is important to initiate important structural rearrangements. In parallel, this network also acts as a nuclear checkpoint machinery that only allows nuclear export, if the PTC and CP has been correctly rearranged.
Publications
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A network of assembly factors involved is involved in remodeling rRNA elements during pre-ribosome maturation J. Cell Biol. 207, 481-98 (2014)
Jochen Baßler, Helge Paternoga, Iris Holdermann, Matthias Thoms, Sander Granneman, Clara Barrio Garcia, Afua Nyarko, Woonghee Lee, Gunther Stier, Sarah A. Clark, Daniel Schraivogel, Martina Kallas, Roland Beckmann, David Tollervey, Elisar Barbar, Irmi Sinning and Ed Hurt
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Coupled GTPase and remodeling ATPase activities form a checkpoint for ribosome export Nature 505, 112-116 (2014)
Yoshitaka Matsuo, Sander Granneman, Matthias Thoms, Rizos- Georgios Manikas, David Tollervey and Ed Hurt
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Architecture of a joint remodelling-checkpoint machinery on the pre-ribosome Nature Struct. Mol. Biol 23, 37-44 (2016)
Clara Barrio-Garcia, Matthias Thoms, Dirk Flemming, Lukas Kater, Jochen Baßler, Roland Beckmann and Ed Hurt
