Powering through ribosome assembly

Abstract

Ribosome assembly is required for cell growth in all organisms. Classic in vitro work in bacteria has led to a detailed understanding of the biophysical, thermodynamic, and structural basis for the ordered and correct assembly of ribosomal proteins on ribosomal RNA. Furthermore, it has enabled reconstitution of active subunits from ribosomal RNA and proteins in vitro. Nevertheless, recent work has shown that eukaryotic ribosome assembly requires a large macromolecular machinery in vivo. Many of these assembly factors such as ATPases, GTPases, and kinases hydrolyze nucleotide triphosphates. Because these enzymes are likely regulatory proteins, much work to date has focused on understanding their role in the assembly process. Here, we review these factors, as well as other sources of energy, and their roles in the ribosome assembly process. In addition, we propose roles of energy-releasing enzymes in the assembly process, to explain why energy is used for a process that occurs largely spontaneously in bacteria. Finally, we use literature data to suggest testable models for how these enzymes could be used as targets for regulation of ribosome assembly.

A Puzzle of Life: Crafting Ribosomal Subunits

“…These assembly and processing events are tightly coupled and occur within preribosomal particles (see Glossary) that travel, as maturation progresses, from the nucleus across nuclear pore complexes (NPCs) to the cytoplasm, where they are ultimately converted into translation-competent ribosomal subunits [5,[9][10][11][12][13] (Figure 2, Key Figure). Given the gargantuan complexity of this process, it is unsurprising that the assembly of eukaryotic ribosomes strictly requires the assistance of a plethora (>200) of mostly essential ribosome biogenesis factors, which are also called trans-acting or assembly factors [5,14,15].…”

60S ribosome biogenesis requires rotation of the 5S ribonucleoprotein particle

“…D uring eukaryotic ribosome formation, a large number of biogenesis factors catalyse the intricate assembly of ribosomal RNA (rRNA) and ribosomal proteins into the two ribosomal subunits [1][2][3][4] . Newly synthesized rRNA folds co-transcriptionally and recruits r-proteins and assembly factors to form the early pre-ribosomal particles, which gradually evolve through a series of intermediates into mature ribosomes [5][6][7][8] .…”

Essential ribosome assembly factor Fap7 regulates a hierarchy of RNA–protein interactions during small ribosomal subunit biogenesis

“…The assembly factors transiently bind to and act on the nascent ribosome in a temporally and spatially well-defined and highly regulated manner. Many of them belong to different classes of GTPases and ATPases (4,5). One peculiar example for such a factor is a protein called Fap7 in Saccharomyces cerevisiae (6) and cofilin interacting protein (hCINAP) or adenylate kinase 6 (hADK6) in humans (7).…”