Abstract
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.
Highlights
Introduction to Eukaryotic Ribosome BiogenesisRibosomes are uniquely crafted to translate the genetic information encoded in mRNA into a polypeptide chain
VCP-like protein 2 (NVL2) in humans, ribosome export/assembly 1 (Rea1), designated Midasin 1 (Mdn1), and diazaborine resistance gene 1 (Drg1), termed spermatogenesis-associated 5 (SPATA5) are all associated with the formation of the large 60S subunit [26]
Defining the structure and composition of these particles has uncovered the metamorphosis of the large ribosomal subunit during maturation; many gaps still remain in the blueprints of ribosome assembly
Summary
Ribosomes are uniquely crafted to translate the genetic information encoded in mRNA into a polypeptide chain. After two processing steps in the 30 ETS of the 35S pre-rRNA, an endonucleolytic cleavage at site A2 within ITS1 separates the maturation pathways of the two ribosomal subunits. (Mdn1), and diazaborine resistance gene 1 (Drg1), termed spermatogenesis-associated 5 (SPATA5) are all associated with the formation of the large 60S subunit [26] This is likely explained by the fact that the maturation cascade of the large subunit involves more individual steps and a larger number of additional assembly factors compared to small subunit maturation. The yeast AAA-ATPases Rix (green), Rea (multi-colored) and Drg (red) associate at different stages of assembly with pre-60S subunits and catalyze the release of specific maturation factors, which are recycled and join freshly produced pre-ribosomes.
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