Structure of the maturing 90S pre-ribosome in association with the RNA exosome

Ribosome assembly is catalyzed by numerous trans-acting factors and coupled with irreversible pre-rRNA processing, driving the pathway toward mature ribosomal subunits. One decisive step early in this progression is removal of the 5' external transcribed spacer (5'-ETS), an RNA extension a...

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Main Authors: Lau, Benjamin (Author) , Cheng, Jingdong (Author) , Flemming, Dirk (Author) , La Venuta, Giuseppe (Author) , Berninghausen, Otto (Author) , Beckmann, Roland (Author) , Hurt, Ed (Author)
Format: Article (Journal)
Language:English
Published: 21 January 2021
In: Molecular cell
Year: 2021, Volume: 81, Issue: 2, Pages: 293-303, e1-e4
ISSN:1097-4164
DOI:10.1016/j.molcel.2020.11.009
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molcel.2020.11.009
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1097276520307875
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Author Notes:Benjamin Lau, Jingdong Cheng, Dirk Flemming, Giuseppe La Venuta, Otto Berninghausen, Roland Beckmann, Ed Hurt

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520 |a Ribosome assembly is catalyzed by numerous trans-acting factors and coupled with irreversible pre-rRNA processing, driving the pathway toward mature ribosomal subunits. One decisive step early in this progression is removal of the 5' external transcribed spacer (5'-ETS), an RNA extension at the 18S rRNA that is integrated into the huge 90S pre-ribosome structure. Upon endo-nucleolytic cleavage at an internal site, A(1), the 5'-ETS is separated from the 18S rRNA and degraded. Here we present biochemical and cryo-electron microscopy analyses that depict the RNA exosome, a major 3'-5' exoribonuclease complex, in a super-complex with the 90S pre-ribosome. The exosome is docked to the 90S through its co-factor Mtr4 helicase, a processive RNA duplex-dismantling helicase, which strategically positions the exosome at the base of 5'-ETS helices H9-H9', which are dislodged in our 90S-exosome structures. These findings suggest a direct role of the exosome in structural remodeling of the 90S pre-ribosome to drive eukaryotic ribosome synthesis. 
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