Special Issue "Ribosome Function and Dynamics"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Organelle Function".

Deadline for manuscript submissions: closed (30 September 2019).

Special Issue Editors

Dr. Martin Koš
E-Mail Website
Guest Editor
Biochemistry Center, Universitat Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
Interests: ribosomal RNA; ribosome biogenesis; RNA modification; snoRNA
Dr. Emma Thomson
E-Mail Website
Guest Editor
Department of Molecular Biology and Biotechnology; Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield S10 2TN, UK
Interests: ribosome biogenesis; nucleolar stress response; RNA exosome complex

Special Issue Information

Dear Colleagues,

Protein translation on ribosomes is an essential, universally conserved process. Perhaps due to this universal nature, the ribosome has long been regarded as a homogenous machine that synthesizes proteins according to the information in mRNA. However, numerous discoveries in recent years contradict this image of a uniform ribosome. High throughput approaches have revealed that both the protein composition and the protein and rRNA modification pattern of ribosomes can differ between cell types, tissues or developmental stages. Collectively these findings have led to the suggestion that “specialized ribosomes” exist. However, the functional consequences of ribosome heterogeneity to translation remain to be established. In addition to ribosome heterogeneity, protein translation has been shown to be regulated by a dynamic tRNA modification and novel noncoding RNAs and tRNA-fragments binding directly to ribosomes. Both protein translation and the synthesis of ribosomes are intrinsically linked to cell growth and proliferation, not only in healthy cells, but also in transformed cancerous cells. This can be visualized in the morphology of the nucleolus, which is frequently used as a marker for cancer. Several ribosomal proteins appear to have noncanonical functions in the nucleolar stress response and regulation of p53 levels and apoptosis. As such ribosome biogenesis has been recognized as an important target for cancer treatment.

The aim of this Special Issue is to bring together the latest knowledge and thus provide a resource of information and perspective that will stimulate future research. We, therefore, invite you to submit reviews and research papers on the topics related to dynamic ribosome composition, function, and regulation.

This may include but is not limited to the following topics:

  • Conservation of ribosomal proteins, RNA and modifications across the kingdoms of life
  • Ribosomal proteins – isoforms, ribosomopathies, and non-ribosomal functions
  • rDNA transcription, rDNA stability, rDNA repeat variability
  • Ribosome biogenesis including the nucleolus structure and phase separation
  • rRNA modifications & snoRNAs
  • Ribosome heterogeneity (specialized ribosomes): protein composition, rRNA sequence variability and rRNA modification
  • Ribosomes/nucleolus and cancer (cause vs consequence, feedback between ribosome biogenesis and cell cycle)
  • Translation regulation (tRNA halfmers and ncRNAs, tRNA modification)
  • Ribosome turnover (ribophagy, ribosome surveillance and quality control)
  • Antibiotics and inhibitors of ribosome biogenesis.
  • Methods to characterize ribosomes, modifications, and translation.

Dr. Martin Koš
Dr. Emma Thomson
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

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Published Papers (11 papers)

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Research

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Open AccessArticle
The Ubiquitin Moiety of Ubi1 Is Required for Productive Expression of Ribosomal Protein eL40 in Saccharomyces cerevisiae
Cells 2019, 8(8), 850; https://doi.org/10.3390/cells8080850 - 07 Aug 2019
Abstract
Ubiquitin is a highly conserved small eukaryotic protein. It is generated by proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor of head-to-tail monomers, or as a single N-terminal moiety to ribosomal proteins. Understanding the [...] Read more.
Ubiquitin is a highly conserved small eukaryotic protein. It is generated by proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor of head-to-tail monomers, or as a single N-terminal moiety to ribosomal proteins. Understanding the role of the ubiquitin fused to ribosomal proteins becomes relevant, as these proteins are practically invariably eS31 and eL40 in the different eukaryotes. Herein, we used the amenable yeast Saccharomyces cerevisiae to study whether ubiquitin facilitates the expression of the fused eL40 (Ubi1 and Ubi2 precursors) and eS31 (Ubi3 precursor) ribosomal proteins. We have analyzed the phenotypic effects of a genomic ubi1∆ub-HA ubi2∆ mutant, which expresses a ubiquitin-free HA-tagged eL40A protein as the sole source of cellular eL40. This mutant shows a severe slow-growth phenotype, which could be fully suppressed by increased dosage of the ubi1∆ub-HA allele, or partially by the replacement of ubiquitin by the ubiquitin-like Smt3 protein. While expression levels of eL40A-HA from ubi1∆ub-HA are low, eL40A is produced practically at normal levels from the Smt3-S-eL40A-HA precursor. Finally, we observed enhanced aggregation of eS31-HA when derived from a Ubi3∆ub-HA precursor and reduced aggregation of eL40A-HA when expressed from a Smt3-S-eL40A-HA precursor. We conclude that ubiquitin might serve as a cis-acting molecular chaperone that assists in the folding and synthesis of the fused eL40 and eS31 ribosomal proteins. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessArticle
Destabilization of Eukaryote mRNAs by 5′ Proximal Stop Codons Can Occur Independently of the Nonsense-Mediated mRNA Decay Pathway
Cells 2019, 8(8), 800; https://doi.org/10.3390/cells8080800 - 31 Jul 2019
Abstract
In eukaryotes, the binding of poly(A) binding protein (PAB) to the poly(A) tail is central to maintaining mRNA stability. PABP interacts with the translation termination apparatus, and with eIF4G to maintain 3′–5′ mRNA interactions as part of an mRNA closed loop. It is [...] Read more.
In eukaryotes, the binding of poly(A) binding protein (PAB) to the poly(A) tail is central to maintaining mRNA stability. PABP interacts with the translation termination apparatus, and with eIF4G to maintain 3′–5′ mRNA interactions as part of an mRNA closed loop. It is however unclear how ribosome recycling on a closed loop mRNA is influenced by the proximity of the stop codon to the poly(A) tail, and how post-termination ribosome recycling affects mRNA stability. We show that in a yeast disabled for nonsense mediated mRNA decay (NMD), a PGK1 mRNA with an early stop codon at codon 22 of the reading frame is still highly unstable, and that this instability cannot be significantly countered even when 50% stop codon readthrough is triggered. In an NMD-deficient mutant yeast, stable reporter alleles with more 3′ proximal stop codons could not be rendered unstable through Rli1-depletion, inferring defective Rli1 ribosome recycling is insufficient in itself to trigger mRNA instability. Mathematical modelling of a translation system including the effect of ribosome recycling and poly(A) tail shortening supports the hypothesis that impaired ribosome recycling from 5′ proximal stop codons may compromise initiation processes and thus destabilize the mRNA. A model is proposed wherein ribosomes undergo a maturation process during early elongation steps, and acquire competency to re-initiate on the same mRNA as translation elongation progresses beyond the very 5′ proximal regions of the mRNA. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessArticle
Functional Analysis of the Ribosomal uL6 Protein of Saccharomyces cerevisiae
Cells 2019, 8(7), 718; https://doi.org/10.3390/cells8070718 - 13 Jul 2019
Abstract
The genome-wide duplication event observed in eukaryotes represents an interesting biological phenomenon, extending the biological capacity of the genome at the expense of the same genetic material. For example, most ribosomal proteins in Saccharomyces cerevisiae are encoded by a pair of paralogous genes. [...] Read more.
The genome-wide duplication event observed in eukaryotes represents an interesting biological phenomenon, extending the biological capacity of the genome at the expense of the same genetic material. For example, most ribosomal proteins in Saccharomyces cerevisiae are encoded by a pair of paralogous genes. It is thought that gene duplication may contribute to heterogeneity of the translational machinery; however, the exact biological function of this event has not been clarified. In this study, we have investigated the functional impact of one of the duplicated ribosomal proteins, uL6, on the translational apparatus together with its consequences for aging of yeast cells. Our data show that uL6 is not required for cell survival, although lack of this protein decreases the rate of growth and inhibits budding. The uL6 protein is critical for the efficient assembly of the ribosome 60S subunit, and the two uL6 isoforms most likely serve the same function, playing an important role in the adaptation of translational machinery performance to the metabolic needs of the cell. The deletion of a single uL6 gene significantly extends the lifespan but only in cells with a high metabolic rate. We conclude that the maintenance of two copies of the uL6 gene enables the cell to cope with the high demands for effective ribosome synthesis. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessArticle
S. cerevisiae Strain Lacking Mitochondrial IF3 Shows Increased Levels of Tma19p during Adaptation to Respiratory Growth
Cells 2019, 8(7), 645; https://doi.org/10.3390/cells8070645 - 26 Jun 2019
Abstract
After billions of years of evolution, mitochondrion retains its own genome, which gets expressed in mitochondrial matrix. Mitochondrial translation machinery rather differs from modern bacterial and eukaryotic cytosolic systems. Any disturbance in mitochondrial translation drastically impairs mitochondrial function. In budding yeast Saccharomyces cerevisiae [...] Read more.
After billions of years of evolution, mitochondrion retains its own genome, which gets expressed in mitochondrial matrix. Mitochondrial translation machinery rather differs from modern bacterial and eukaryotic cytosolic systems. Any disturbance in mitochondrial translation drastically impairs mitochondrial function. In budding yeast Saccharomyces cerevisiae, deletion of the gene coding for mitochondrial translation initiation factor 3—AIM23, leads to an imbalance in mitochondrial protein synthesis and significantly delays growth after shifting from fermentable to non-fermentable carbon sources. Molecular mechanism underlying this adaptation to respiratory growth was unknown. Here, we demonstrate that slow adaptation from glycolysis to respiration in the absence of Aim23p is accompanied by a gradual increase of cytochrome c oxidase activity and by increased levels of Tma19p protein, which protects mitochondria from oxidative stress. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessArticle
A Versatile Strategy to Reduce UGA-Selenocysteine Recoding Efficiency of the Ribosome Using CRISPR-Cas9-Viral-Like-Particles Targeting Selenocysteine-tRNA[Ser]Sec Gene
Cells 2019, 8(6), 574; https://doi.org/10.3390/cells8060574 - 11 Jun 2019
Abstract
The translation of selenoprotein mRNAs involves a non-canonical ribosomal event in which an in-frame UGA is recoded as a selenocysteine (Sec) codon instead of being read as a stop codon. The recoding machinery is centered around two dedicated RNA components: The selenocysteine insertion [...] Read more.
The translation of selenoprotein mRNAs involves a non-canonical ribosomal event in which an in-frame UGA is recoded as a selenocysteine (Sec) codon instead of being read as a stop codon. The recoding machinery is centered around two dedicated RNA components: The selenocysteine insertion sequence (SECIS) located in the 3′ UTR of the mRNA and the selenocysteine-tRNA (Sec-tRNA[Ser]Sec). This translational UGA-selenocysteine recoding event by the ribosome is a limiting stage of selenoprotein expression. Its efficiency is controlled by the SECIS, the Sec-tRNA[Ser]Sec and their interacting protein partners. In the present work, we used a recently developed CRISPR strategy based on murine leukemia virus-like particles (VLPs) loaded with Cas9-sgRNA ribonucleoproteins to inactivate the Sec-tRNA[Ser]Sec gene in human cell lines. We showed that these CRISPR-Cas9-VLPs were able to induce efficient genome-editing in Hek293, HepG2, HaCaT, HAP1, HeLa, and LNCaP cell lines and this caused a robust reduction of selenoprotein expression. The alteration of selenoprotein expression was the direct consequence of lower levels of Sec-tRNA[Ser]Sec and thus a decrease in translational recoding efficiency of the ribosome. This novel strategy opens many possibilities to study the impact of selenoprotein deficiency in hard-to-transfect cells, since these CRISPR-Cas9-VLPs have a wide tropism. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Review

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Open AccessReview
An Update on Mitochondrial Ribosome Biology: The Plant Mitoribosome in the Spotlight
Cells 2019, 8(12), 1562; https://doi.org/10.3390/cells8121562 - 03 Dec 2019
Abstract
Contrary to the widely held belief that mitochondrial ribosomes (mitoribosomes) are highly similar to bacterial ones, recent experimental evidence reveals that mitoribosomes do differ significantly from their bacterial counterparts. This review is focused on plant mitoribosomes, but we also highlight the most striking [...] Read more.
Contrary to the widely held belief that mitochondrial ribosomes (mitoribosomes) are highly similar to bacterial ones, recent experimental evidence reveals that mitoribosomes do differ significantly from their bacterial counterparts. This review is focused on plant mitoribosomes, but we also highlight the most striking similarities and differences between the plant and non-plant mitoribosomes. An analysis of the composition and structure of mitoribosomes in trypanosomes, yeast, mammals and plants uncovers numerous organism-specific features. For the plant mitoribosome, the most striking feature is the enormous size of the small subunit compared to the large one. Apart from the new structural information, possible functional peculiarities of different types of mitoribosomes are also discussed. Studies suggest that the protein composition of mitoribosomes is dynamic, especially during development, giving rise to a heterogeneous populations of ribosomes fulfilling specific functions. Moreover, convincing data shows that mitoribosomes interact with components involved in diverse mitochondrial gene expression steps, forming large expressosome-like structures. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
Open AccessFeature PaperReview
The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation
Cells 2019, 8(11), 1379; https://doi.org/10.3390/cells8111379 - 02 Nov 2019
Abstract
The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be chemically modified by reactive oxygen species, which may alter the ribosome′s functions or cause a complete loss of functionality. The [...] Read more.
The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be chemically modified by reactive oxygen species, which may alter the ribosome′s functions or cause a complete loss of functionality. The oxidative damage that ribosomes accumulate during their lifespan in a cell may lead to reduced or faulty translation and contribute to various pathologies. However, remarkably little is known about the biological consequences of oxidative damage to the ribosome. Here, we provide a concise summary of the known types of changes induced by reactive oxygen species in rRNA and ribosomal proteins and discuss the existing experimental evidence of how these modifications may affect ribosome dynamics and function. We emphasize the special role that redox-active transition metals, such as iron, play in ribosome homeostasis and stability. We also discuss the hypothesis that redox-mediated ribosome modifications may contribute to adaptive cellular responses to stress. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessReview
The Impact of the Stringent Response on TRAFAC GTPases and Prokaryotic Ribosome Assembly
Cells 2019, 8(11), 1313; https://doi.org/10.3390/cells8111313 - 24 Oct 2019
Abstract
Many facets of ribosome biogenesis and function, including ribosomal RNA (rRNA) transcription, 70S assembly and protein translation, are negatively impacted upon induction of a nutrient stress-sensing signalling pathway termed the stringent response. This stress response is mediated by the alarmones guanosine tetra- and [...] Read more.
Many facets of ribosome biogenesis and function, including ribosomal RNA (rRNA) transcription, 70S assembly and protein translation, are negatively impacted upon induction of a nutrient stress-sensing signalling pathway termed the stringent response. This stress response is mediated by the alarmones guanosine tetra- and penta-phosphate ((p)ppGpp), the accumulation of which leads to a massive cellular response that slows growth and aids survival. The 70S bacterial ribosome is an intricate structure, with assembly both complex and highly modular. Presiding over the assembly process is a group of P-loop GTPases within the TRAFAC (Translation Factor Association) superclass that are crucial for correct positioning of both early and late stage ribosomal proteins (r-proteins) onto the rRNA. Often described as ‘molecular switches’, members of this GTPase superfamily readily bind and hydrolyse GTP to GDP in a cyclic manner that alters the propensity of the GTPase to carry out a function. TRAFAC GTPases are considered to act as checkpoints to ribosome assembly, involved in binding to immature sections in the GTP-bound state, preventing further r-protein association until maturation is complete. Here we review our current understanding of the impact of the stringent response and (p)ppGpp production on ribosome maturation in prokaryotic cells, focusing on the inhibition of (p)ppGpp on GTPase-mediated subunit assembly, but also touching upon the inhibition of rRNA transcription and protein translation. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessReview
The Expanding Riboverse
Cells 2019, 8(10), 1205; https://doi.org/10.3390/cells8101205 - 05 Oct 2019
Abstract
Subverting the conventional concept of “the” ribosome, a wealth of information gleaned from recent studies is revealing a much more diverse and dynamic ribosomal reality than has traditionally been thought possible. A diverse array of researchers is collectively illuminating a universe of heterogeneous [...] Read more.
Subverting the conventional concept of “the” ribosome, a wealth of information gleaned from recent studies is revealing a much more diverse and dynamic ribosomal reality than has traditionally been thought possible. A diverse array of researchers is collectively illuminating a universe of heterogeneous and adaptable ribosomes harboring differences in composition and regulatory capacity: These differences enable specialization. The expanding universe of ribosomes not only comprises an incredible richness in ribosomal specialization between species, but also within the same tissues and even cells. In this review, we discuss ribosomal heterogeneity and speculate how the emerging understanding of the ribosomal repertoire is impacting the biological sciences today. Targeting pathogen-specific and pathological “diseased” ribosomes promises to provide new treatment options for patients, and potential applications for “designer ribosomes” are within reach. Our deepening understanding of and ability to manipulate the ribosome are establishing both the technological and theoretical foundations for major advances for the 21st century and beyond. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessReview
How Cancer Exploits Ribosomal RNA Biogenesis: A Journey beyond the Boundaries of rRNA Transcription
Cells 2019, 8(9), 1098; https://doi.org/10.3390/cells8091098 - 17 Sep 2019
Abstract
The generation of new ribosomes is a coordinated process essential to sustain cell growth. As such, it is tightly regulated according to cell needs. As cancer cells require intense protein translation to ensure their enhanced growth rate, they exploit various mechanisms to boost [...] Read more.
The generation of new ribosomes is a coordinated process essential to sustain cell growth. As such, it is tightly regulated according to cell needs. As cancer cells require intense protein translation to ensure their enhanced growth rate, they exploit various mechanisms to boost ribosome biogenesis. In this review, we will summarize how oncogenes and tumor suppressors modulate the biosynthesis of the RNA component of ribosomes, starting from the description of well-characterized pathways that converge on ribosomal RNA transcription while including novel insights that reveal unexpected regulatory networks hacked by cancer cells to unleash ribosome production. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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Open AccessReview
Regulation of Ribosomal Proteins on Viral Infection
by Shuo Li
Cells 2019, 8(5), 508; https://doi.org/10.3390/cells8050508 - 27 May 2019
Cited by 1
Abstract
Ribosomal proteins (RPs), in conjunction with rRNA, are major components of ribosomes involved in the cellular process of protein biosynthesis, known as “translation”. The viruses, as the small infectious pathogens with limited genomes, must recruit a variety of host factors to survive and [...] Read more.
Ribosomal proteins (RPs), in conjunction with rRNA, are major components of ribosomes involved in the cellular process of protein biosynthesis, known as “translation”. The viruses, as the small infectious pathogens with limited genomes, must recruit a variety of host factors to survive and propagate, including RPs. At present, more and more information is available on the functional relationship between RPs and virus infection. This review focuses on advancements in my own understanding of critical roles of RPs in the life cycle of viruses. Various RPs interact with viral mRNA and proteins to participate in viral protein biosynthesis and regulate the replication and infection of virus in host cells. Most interactions are essential for viral translation and replication, which promote viral infection and accumulation, whereas the minority represents the defense signaling of host cells by activating immune pathway against virus. RPs provide a new platform for antiviral therapy development, however, at present, antiviral therapeutics with RPs involving in virus infection as targets is limited, and exploring antiviral strategy based on RPs will be the guides for further study. Full article
(This article belongs to the Special Issue Ribosome Function and Dynamics)
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