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A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation
Authors:Jochen Ba?ler  Helge Paternoga  Iris Holdermann  Matthias Thoms  Sander Granneman  Clara Barrio-Garcia  Afua Nyarko  Gunter Stier  Sarah A Clark  Daniel Schraivogel  Martina Kallas  Roland Beckmann  David Tollervey  Elisar Barbar  Irmi Sinning  Ed Hurt
Institution:1Biochemistry Center of Heidelberg University, INF328, D-69120 Heidelberg, Germany;2Centre for Synthetic and Systems Biology (SynthSys), and 3Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK;4Gene Center, Department of Chemistry and Biochemistry, University of Munich, 80539 Munich, Germany;5Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331
Abstract:Eukaryotic ribosome biogenesis involves ∼200 assembly factors, but how these contribute to ribosome maturation is poorly understood. Here, we identify a network of factors on the nascent 60S subunit that actively remodels preribosome structure. At its hub is Rsa4, a direct substrate of the force-generating ATPase Rea1. We show that Rsa4 is connected to the central protuberance by binding to Rpl5 and to ribosomal RNA (rRNA) helix 89 of the nascent peptidyl transferase center (PTC) through Nsa2. Importantly, Nsa2 binds to helix 89 before relocation of helix 89 to the PTC. Structure-based mutations of these factors reveal the functional importance of their interactions for ribosome assembly. Thus, Rsa4 is held tightly in the preribosome and can serve as a “distribution box,” transmitting remodeling energy from Rea1 into the developing ribosome. We suggest that a relay-like factor network coupled to a mechano-enzyme is strategically positioned to relocate rRNA elements during ribosome maturation.
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