Eukaryotic ribosome assembly, transport and quality control

Peña, Cohue; Hurt, Ed; Panse, Vikram Govind

doi:10.1038/nsmb.3454

Cited by 211 publications

(188 citation statements)

References 99 publications

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Parker

Collins

Korona

et al. 2019

Preprint

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Premature release of nascent ribosomes into the translating pool must be prevented, as these do not support viability and may be prone to mistakes. Here we show that the kinase Rio1, the nuclease Nob1, and its binding partner Pno1 cooperate to establish a checkpoint that prevents the escape of immature ribosomes into polysomes. Nob1 blocks mRNA recruitment, and rRNA cleavage is required for its dissociation from nascent 40S subunits, thereby setting up a checkpoint for maturation. Rio1 releases Nob1 and Pno1 from pre-40S ribosomes to discharge nascent 40S into the translating pool. Weakly binding Nob1 and Pno1 mutants can bypass the requirement for Rio1, and Pno1 mutants rescue cell viability. In these strains, immature ribosomes escape into the translating pool, where they cause fidelity defects and perturb protein homeostasis. Thus, the Rio1-Nob1-Pno1 network establishes a checkpoint that safeguards against the release of immature ribosomes into the translating pool.

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Section: Introductionmentioning

confidence: 99%

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

Parker

Collins

Korona

et al. 2019

Preprint

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“…The substoichiometric presence of eS25 and other RPs on cellular ribosomes tempts the possibility that such compositional alterations are selected for translational control and participate in cellular functions such as tissue diversification (Shi et al, 2017). Yet it is still unclear how and why a cell would produce such heterogeneity given the complex and energy expensive nature of ribosome biogenesis (Klinge and Woolford, 2019;Peña et al, 2017). Potentially supporting this interpretation, a recent study found that maternal ribosomes are sufficient for embryogenesis in C. elegans (Cenik et al, 2019), meaning that functional ribosome heterogeneity in embryonic cell types must occur after assembly and transport.…”

Section: Discussionmentioning

confidence: 99%

“…RPs do much more than chaperone rRNA maturation concordant with their assembly, and several biogenesis checkpoints exist, providing opportunities for feedback loops to sense proper assembly (Klinge and Woolford, 2019;Peña et al, 2017). The complexity of ribosome biogenesis in eukaryotes is amplified by the existence of the nucleolus-a subnuclear, membraneless organelle that is a key hub for stress sensing (Boulon et al, 2010;Yang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

A memory of RPS25 loss drives resistance phenotypes

Johnson

Flynn

Lapointe

et al. 2019

Preprint

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In order to maintain cellular protein homeostasis, ribosomes are safeguarded against dysregulation by myriad processes. Remarkably, many cell types can withstand the genetic disruption of numerous ribosomal protein genes, indicating that select ribosome variants can sustain cellular life. Genetic alterations of ribosomal protein genes have been further linked to diverse cellular phenotypes and human disease, yet the direct and indirect consequences of sustained alterations in ribosomal protein levels are poorly understood. To address this knowledge gap, we studied in vitro and cellular consequences that follow genetic knockout of the small subunit ribosomal proteins RPS25 or RACK1 in a human haploid cell line. To our surprise, we found that multiple cellular phenotypes previously assumed to result from a direct effect on translation were instead caused by indirect effects. During characterization of ribosomes isolated from the RPS25 knockout cell line, we discovered a partial remodeling of the large subunit via the ribosomal protein paralog eL22L1. Upon further examination, we found that RPS25 knockout clones display irreversible rewiring of viral-and toxin-resistance phenotypes, suggesting that the cells had undergone a stable transition to a new cell state. This new state appears to drive pleiotropic phenotypes and is characterized by a dramatically altered transcriptome and membrane proteome. By homology-directed repair of a RPS25 knockout cell line, we demonstrate that even when RPS25 expression is rescued at the native genomic locus, cells fail to correct for the phenotypic hysteresis. Our results illustrate how the elasticity of cells to a ribosome perturbation can manifest as specific but indirect phenotypic outcomes. The eukaryotic ribosome is comprised of four strands of rRNA and ~80 ribosomal proteins (RPs)

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“…Ribosome biogenesis is the best-characterized and primary function of the nucleolus and consists of a series of highly coordinated processes involving diverse factors at different levels. 34 Nucleolus size is also positively associated with rDNA transcription. 35 Because the size and structure of the nucleolus was disrupted upon NOP2 KD as shown above ( Figure 5A), we first quantify the level of ribosome RNAs at the eight-cell stage.…”

Section: Nop2 Depletion Inhibits Ribosome Biogenesis During Preimplmentioning

confidence: 98%

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

Wang

et al. 2019

FASEB j.

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The maternal nucleolus plays an indispensable role in zygotic genome activation (ZGA) and early embryonic development in mice. During oocyte-to-embryo transition, the nucleolus is subject to substantial transformation. Despite the primary role of the nucleolus is ribosome biogenesis, accumulating evidence has uncovered its functions in various other cell processes. However, the regulation of nucleolar maturation and ribosome biogenesis and the molecules involved remain unclear during early embryonic development. In this study, we observed that nucleolar protein 2 (NOP2) is restrictedly localized within the nucleolus, first detected in the late two-cell embryos, and increases to a peak level at the eight-cell stage in mice. RNAi-mediated NOP2 depletion leads to a developmental arrest during the morula-to-blastocyst transition. RNA-seq analyses reveal that 208 genes are differentially expressed, including multiple lineage-specific genes and several genes encoding ribosome proteins.Indeed, we observe a failure of the first lineage specification with reduced TEA domain transcription factor 4(TEAD4) (trophectoderm-specific), tir na nog (NANOG), and kruppel-like factor 4 (KLF4) (inner cell mass-specific). Importantly, by Transm ission Electron Microscopy (TEM), we noted a decrease in the ratio of the nucleolus size and an increase in the ratio of the size of the nucleolus precursor body, suggesting the nucleolar maturation is disrupted. Moreover, both qPCR and Fluorescence I n Situ Hybridization (FISH) data showcase a significant decrease in the abundance of ribosome RNAs. Similarly, NOP2 depletion causes reduced developmental potential and decreased rRNA level in bovine early embryos, suggesting a functional 2716 |

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Eukaryotic ribosome assembly, transport and quality control

Cited by 211 publications

References 99 publications

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

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

A memory of RPS25 loss drives resistance phenotypes

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

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