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Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis

1
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/EG, Graz A-8010, Austria
2
Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, Durham, NC 27709, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Biomolecules 2019, 9(11), 715; https://doi.org/10.3390/biom9110715
Received: 9 October 2019 / Revised: 4 November 2019 / Accepted: 5 November 2019 / Published: 7 November 2019
AAA-ATPases are molecular engines evolutionarily optimized for the remodeling of proteins and macromolecular assemblies. Three AAA-ATPases are currently known to be involved in the remodeling of the eukaryotic ribosome, a megadalton range ribonucleoprotein complex responsible for the translation of mRNAs into proteins. The correct assembly of the ribosome is performed by a plethora of additional and transiently acting pre-ribosome maturation factors that act in a timely and spatially orchestrated manner. Minimal disorder of the assembly cascade prohibits the formation of functional ribosomes and results in defects in proliferation and growth. Rix7, Rea1, and Drg1, which are well conserved across eukaryotes, are involved in different maturation steps of pre-60S ribosomal particles. These AAA-ATPases provide energy for the efficient removal of specific assembly factors from pre-60S particles after they have fulfilled their function in the maturation cascade. Recent structural and functional insights have provided the first glimpse into the molecular mechanism of target recognition and remodeling by Rix7, Rea1, and Drg1. Here we summarize current knowledge on the AAA-ATPases involved in eukaryotic ribosome biogenesis. We highlight the latest insights into their mechanism of mechano-chemical complex remodeling driven by advanced cryo-EM structures and the use of highly specific AAA inhibitors.
Keywords: AAA-ATPases; ribosome biogenesis; Rix7/NVL2; Rea1/Mdn1; Drg1/SPATA5; substrate processing; cryo-EM; small molecular weight inhibitors AAA-ATPases; ribosome biogenesis; Rix7/NVL2; Rea1/Mdn1; Drg1/SPATA5; substrate processing; cryo-EM; small molecular weight inhibitors
MDPI and ACS Style

Prattes, M.; Lo, Y.-H.; Bergler, H.; Stanley, R.E. Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis. Biomolecules 2019, 9, 715.

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