A Puzzle of Life: Crafting Ribosomal Subunits

Abstract

The biogenesis of eukaryotic ribosomes is a complicated process during which the transcription, modification, folding, and processing of the rRNA is coupled with the ordered assembly of $80 ribosomal proteins (r-proteins). Ribosome synthesis is catalyzed and coordinated by more than 200 biogenesis factors as the preribosomal subunits acquire maturity on their path from the nucleolus to the cytoplasm. Several biogenesis factors also interconnect the progression of ribosome assembly with quality control of important domains, ensuring that only functional subunits engage in translation. With the recent visualization of several assembly intermediates by cryoelectron microscopy (cryo-EM), a structural view of ribosome assembly begins to emerge. In this review we integrate these first structural insights into an updated overview of the consecutive ribosome assembly steps. Synopsis of Eukaryotic Ribosome AssemblyRibosomes are the molecular machines that translate the genetic information from the intermediary mRNA templates into proteins [1]. Eukaryotic 80S ribosomes comprise two unequal subunits that contain four different rRNAs and around 80 r-proteins ( Figure 1). The small 40S subunit (SSU) comprises the 18S rRNA and 33 r-proteins (referred to as RPS or S). The large 60S subunit (LSU) comprises the 25S/28S, 5.8S, and 5S rRNA and, in most eukaryotic species, 47 r-proteins (RPL or L); a notable exception is budding yeasts, which lack eL28The act of building a ribosome begins in the nucleolus, where the ribosomal DNA (rDNA) is transcribed into a long pre-rRNA precursor (35S pre-rRNA in yeast) and involves the ordered assembly of the r-proteins with the pre-rRNA, which is concomitantly processed into the mature rRNA species [5][6][7][8] (Figure 1 and Box 1). 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].Our current knowledge has been mainly obtained by studying ribosome biogenesis in the yeast Saccharomyces cerevisiae. Research conducted in the 1970s defined the r-protein composition of ribosomes, revealed the major pre-rRNA processing intermediates, and uncovered the existence of the 90S, 43S, and 66S preribosomal particles. The following 25 years witnessed the identification of numerous biogenesis factors and attributed functional roles TrendsCryoelectron microscopy analyses of the 90S preribosome show that the biogenesis factors create a casting mold that encloses the nascent pre-40S subunit.Structures of nuclear pre-60S particles reveal that a...

A kinase-dependent checkpoint prevents escape of immature ribosomes into the translating pool

“…Ribosome assembly is a highly regulated process, involving the proper folding and processing of 4 rRNAs, as well as binding of 79 ribosomal proteins (r-proteins). Assembly is facilitated by over 200 transiently binding assembly factors that promote assembly and quality control, and prevent immature ribosomes from initiating translation prematurely (Kressler et al, 2017;Pena et al, 2017;Warner, 1999;Woolford and Baserga, 2013).…”

Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence

“…Mammalian ribosomes are nucleoprotein complexes comprised of a large (60S) subunit and a small (40S) subunit that carry out the fundamental process of translation. The mature ribosome contains four ribosomal RNAs (rRNAs) and almost 80 proteins and the complex process of ribosome biogenesis involves over 200 trans-acting factors (reviewed in (Kressler, Hurt, & Baßler, 2017)). Transcription of rRNA precursors from tandem repeats of ribosomal DNA (rDNA) initiates ribosome biogenesis and a complex sequence of events including sequential splicing and recruitment of rRNA-associated proteins ensues.…”

The nucleolar protein NOP2 is required for nucleolar maturation and ribosome biogenesis during preimplantation development in mammals

“…NOP2 is not required for preimplantation development 5-Methylcytosine (m5C) is a common RNA modification that takes place in a variety of RNA species, including rRNAs. Indeed, a recent study confirmed the presence of m5C in human rRNAs, although its biological role remains unclear.…”

“…A functional ribosome is a delicate molecular machine composed of 60S large subunit and 40S small subunit, each of them built from ribosome RNAs (rRNAs) and numerous ribosome proteins. 5,6 Ribosome biogenesis consists of a series of highly coordinated and energy demanding processes, involving a large number of factors and pathways. 7 It starts in the nucleolus, where rRNAs were transcribed by RNA polymerase I (RNA Pol I).…”