Ribosomal Proteins in Ribosome Assembly

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Structure and Dynamics".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 13272

Special Issue Editors

Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
Interests: ribosome assembly; ribosomal proteins; ribosome assembly factors; dedicated ribosomal protein chaperones
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria
Interests: ribosome assembly; ribosomal proteins; ribosome assembly factors; dedicated ribosomal protein chaperones

Special Issue Information

Dear Colleagues,

Ribosome biogenesis is a key cellular process involving the assembly of ribosomal proteins (r-proteins) with ribosomal RNA (rRNA) into the complex three-dimensional structure of mature ribosomes. However, the cell has to invest resources and energy even before r-proteins join with rRNA. Newly synthesized r-proteins are prone to aggregation and therefore need to be protected both by the general cellular chaperone network and by dedicated r-protein chaperones that counteract aggregation of individual r-proteins. Eukaryotic r-proteins, moreover, have to overcome a physical obstacle: they are synthesized in the cytoplasm, but most of them are incorporated into pre-ribosomal particles in the nucleolus, the site of rRNA transcription. Hence, eukaryotic ribosome biogenesis relies on the efficient nuclear import of r-proteins.

Many r-proteins bind rRNA already co-transcriptionally, concomitantly with the folding of the emerging rRNA into a defined secondary structure. rRNA folding and r-protein binding are strongly interdependent processes, with rRNA folding generating binding sites for r-proteins that facilitate further rRNA folding and therefore create binding sites for later binding proteins. In many cases, r-proteins have composite binding sites comprising different rRNA domains and are accommodated into the ribosomal particle with an initial weak binding being further strengthened during ribosome biogenesis as the r-proteins establish their cognate interactions.

Mutation or depletion of almost any r-protein leads to a distinct ribosome assembly defect. In line with that, mutations in human r-proteins can lead to diseases, so-called ribosomopathies. Moreover, r-proteins accumulating upon delayed ribosome assembly can function as regulators of tumor suppressor p53, hence providing a link between r-proteins, ribosome biogenesis, and cancer.  

This issue aims to present up-to-date original research manuscripts as well as review manuscripts about all aspects of r-proteins in ribosome assembly, including insights from all domains of life that cover but are not restricted to the following areas:

  • Regulation of r-protein synthesis;
  • Nuclear import of r-proteins and r-protein chaperones;
  • The order and mechanisms of incorporation of r-proteins into nascent ribosomes;
  • The functions of r-proteins in rRNA folding and ribosome maturation;
  • Evolutionary aspects—r-proteins in bacteria, archaea, and eukaryotes;
  • Diseases of aberrant r-protein synthesis and assembly.

Dr. Brigitte Pertschy
Dr. Ingrid Zierler
Guest Editors

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Keywords

  • ribosome assembly
  • ribosomal protein (r-protein)
  • ribosomal RNA (rRNA)
  • rRNA folding
  • ribosome assembly factors
  • dedicated r-protein chaperones
  • ribosomopathies

Published Papers (8 papers)

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Research

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23 pages, 3039 KiB  
Article
Loss of the DYRK1A Protein Kinase Results in the Reduction in Ribosomal Protein Gene Expression, Ribosome Mass and Reduced Translation
by Chiara Di Vona, Laura Barba, Roberto Ferrari and Susana de la Luna
Biomolecules 2024, 14(1), 31; https://doi.org/10.3390/biom14010031 - 25 Dec 2023
Cited by 1 | Viewed by 784
Abstract
Ribosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated to ensure the appropriate assembly of ribosomes and to respond to the growth demands of cells. The elements regulating the transcription of RP genes [...] Read more.
Ribosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated to ensure the appropriate assembly of ribosomes and to respond to the growth demands of cells. The elements regulating the transcription of RP genes (RPGs) have been characterized in yeast and Drosophila, yet how cells regulate the production of RPs in mammals is less well understood. Here, we show that a subset of RPG promoters is characterized by the presence of the palindromic TCTCGCGAGA motif and marked by the recruitment of the protein kinase DYRK1A. The presence of DYRK1A at these promoters is associated with the enhanced binding of the TATA-binding protein, TBP, and it is negatively correlated with the binding of the GABP transcription factor, establishing at least two clusters of RPGs that could be coordinately regulated. However, DYRK1A silencing leads to a global reduction in RPGs mRNAs, pointing at DYRK1A activities beyond those dependent on its chromatin association. Significantly, cells in which DYRK1A is depleted have reduced RP levels, fewer ribosomes, reduced global protein synthesis and a smaller size. We therefore propose a novel role for DYRK1A in coordinating the expression of genes encoding RPs, thereby controlling cell growth in mammals. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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17 pages, 2016 KiB  
Article
Differential Participation of Plant Ribosomal Proteins from the Small Ribosomal Subunit in Protein Translation under Stress
by Zainab Fakih, Mélodie B. Plourde and Hugo Germain
Biomolecules 2023, 13(7), 1160; https://doi.org/10.3390/biom13071160 - 21 Jul 2023
Cited by 2 | Viewed by 1467
Abstract
Upon exposure to biotic and abiotic stress, plants have developed strategies to adapt to the challenges imposed by these unfavorable conditions. The energetically demanding translation process is one of the main elements regulated to reduce energy consumption and to selectively synthesize proteins involved [...] Read more.
Upon exposure to biotic and abiotic stress, plants have developed strategies to adapt to the challenges imposed by these unfavorable conditions. The energetically demanding translation process is one of the main elements regulated to reduce energy consumption and to selectively synthesize proteins involved in the establishment of an adequate response. Emerging data have shown that ribosomes remodel to adapt to stresses. In Arabidopsis thaliana, ribosomes consist of approximately eighty-one distinct ribosomal proteins (RPs), each of which is encoded by two to seven genes. Recent research has revealed that a mutation in a given single RP in plants can not only affect the functions of the RP itself but can also influence the properties of the ribosome, which could bring about changes in the translation to varying degrees. However, a pending question is whether some RPs enable ribosomes to preferentially translate specific mRNAs. To reveal the role of ribosomal proteins from the small subunit (RPS) in a specific translation, we developed a novel approach to visualize the effect of RPS silencing on the translation of a reporter mRNA (GFP) combined to the 5’UTR of different housekeeping and defense genes. The silencing of genes encoding for NbRPSaA, NbRPS5A, and NbRPS24A in Nicotiana benthamiana decreased the translation of defense genes. The NbRACK1A-silenced plant showed compromised translations of specific antioxidant enzymes. However, the translations of all tested genes were affected in NbRPS27D-silenced plants. These findings suggest that some RPS may be potentially involved in the control of protein translation. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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21 pages, 4702 KiB  
Article
Dissecting the Nuclear Import of the Ribosomal Protein Rps2 (uS5)
by Andreas Steiner, Sébastien Favre, Maximilian Mack, Annika Hausharter, Benjamin Pillet, Jutta Hafner, Valentin Mitterer, Dieter Kressler, Brigitte Pertschy and Ingrid Zierler
Biomolecules 2023, 13(7), 1127; https://doi.org/10.3390/biom13071127 - 14 Jul 2023
Viewed by 1020
Abstract
The ribosome is assembled in a complex process mainly taking place in the nucleus. Consequently, newly synthesized ribosomal proteins have to travel from the cytoplasm into the nucleus, where they are incorporated into nascent ribosomal subunits. In this study, we set out to [...] Read more.
The ribosome is assembled in a complex process mainly taking place in the nucleus. Consequently, newly synthesized ribosomal proteins have to travel from the cytoplasm into the nucleus, where they are incorporated into nascent ribosomal subunits. In this study, we set out to investigate the mechanism mediating nuclear import of the small subunit ribosomal protein Rps2. We demonstrate that an internal region in Rps2, ranging from amino acids 76 to 145, is sufficient to target a 3xyEGFP reporter to the nucleus. The importin-β Pse1 interacts with this Rps2 region and is involved in its import, with Rps2 residues arginine 95, arginine 97, and lysine 99 being important determinants for both Pse1 binding and nuclear localization. Moreover, our data reveal a second import mechanism involving the N-terminal region of Rps2, which depends on the presence of basic residues within amino acids 10 to 28. This Rps2 segment overlaps with the binding site of the dedicated chaperone Tsr4; however, the nuclear import of Rps2 via the internal as well as the N-terminal nuclear-targeting element does not depend on Tsr4. Taken together, our study has unveiled hitherto undescribed nuclear import signals, showcasing the versatility of the mechanisms coordinating the nuclear import of ribosomal proteins. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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13 pages, 3156 KiB  
Article
Ribosomal Protein S12 Hastens Nucleation of Co-Transcriptional Ribosome Assembly
by Margaret L. Rodgers, Yunsheng Sun and Sarah A. Woodson
Biomolecules 2023, 13(6), 951; https://doi.org/10.3390/biom13060951 - 06 Jun 2023
Cited by 1 | Viewed by 1129
Abstract
Ribosomal subunits begin assembly during transcription of the ribosomal RNA (rRNA), when the rRNA begins to fold and associate with ribosomal proteins (RPs). In bacteria, the first steps of ribosome assembly depend upon recognition of the properly folded rRNA by primary assembly proteins [...] Read more.
Ribosomal subunits begin assembly during transcription of the ribosomal RNA (rRNA), when the rRNA begins to fold and associate with ribosomal proteins (RPs). In bacteria, the first steps of ribosome assembly depend upon recognition of the properly folded rRNA by primary assembly proteins such as S4, which nucleates assembly of the 16S 5′ domain. Recent evidence, however, suggests that initial recognition by S4 is delayed due to variable folding of the rRNA during transcription. Here, using single-molecule colocalization co-transcriptional assembly (smCoCoA), we show that the late-binding RP S12 specifically promotes the association of S4 with the pre-16S rRNA during transcription, thereby accelerating nucleation of 30S ribosome assembly. Order of addition experiments suggest that S12 helps chaperone the rRNA during transcription, particularly near the S4 binding site. S12 interacts transiently with the rRNA during transcription and, consequently, a high concentration is required for its chaperone activity. These results support a model in which late-binding RPs moonlight as RNA chaperones during transcription in order to facilitate rapid assembly. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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18 pages, 4149 KiB  
Article
RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling
by Matthew John Eastham, Andria Pelava, Graeme Raymond Wells, Nicholas James Watkins and Claudia Schneider
Biomolecules 2023, 13(6), 898; https://doi.org/10.3390/biom13060898 - 28 May 2023
Viewed by 1629
Abstract
Two of the four human ubiquitin-encoding genes express ubiquitin as an N-terminal fusion precursor polypeptide, with either ribosomal protein (RP) RPS27a or RPL40 at the C-terminus. RPS27a and RPL40 have been proposed to be important for the induction of the tumour suppressor p53 [...] Read more.
Two of the four human ubiquitin-encoding genes express ubiquitin as an N-terminal fusion precursor polypeptide, with either ribosomal protein (RP) RPS27a or RPL40 at the C-terminus. RPS27a and RPL40 have been proposed to be important for the induction of the tumour suppressor p53 in response to defects in ribosome biogenesis, suggesting that they may play a role in the coordination of ribosome production, ubiquitin levels and p53 signalling. Here, we report that RPS27a is cleaved from the ubiquitin-RP precursor in a process that appears independent of ribosome biogenesis. In contrast to other RPs, the knockdown of either RPS27a or RPL40 did not stabilise the tumour suppressor p53 in U2OS cells. Knockdown of neither protein blocked p53 stabilisation following inhibition of ribosome biogenesis by actinomycin D, indicating that they are not needed for p53 signalling in these cells. However, the knockdown of both RPS27a and RPL40 in MCF7 and LNCaP cells robustly induced p53, consistent with observations made with the majority of other RPs. Importantly, RPS27a and RPL40 are needed for rRNA production in all cell lines tested. Our data suggest that the role of RPS27a and RPL40 in p53 signalling, but not their importance in ribosome biogenesis, differs between cell types. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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16 pages, 9892 KiB  
Article
Structural Insights into the Distortion of the Ribosomal Small Subunit at Different Magnesium Concentrations
by Ting Yu, Junyi Jiang, Qianxi Yu, Xin Li and Fuxing Zeng
Biomolecules 2023, 13(3), 566; https://doi.org/10.3390/biom13030566 - 20 Mar 2023
Cited by 1 | Viewed by 1903
Abstract
Magnesium ions are abundant and play indispensable functions in the ribosome. A decrease in Mg2+ concentration causes 70S ribosome dissociation and subsequent unfolding. Structural distortion at low Mg2+ concentrations has been observed in an immature pre50S, while the structural changes in [...] Read more.
Magnesium ions are abundant and play indispensable functions in the ribosome. A decrease in Mg2+ concentration causes 70S ribosome dissociation and subsequent unfolding. Structural distortion at low Mg2+ concentrations has been observed in an immature pre50S, while the structural changes in mature subunits have not yet been studied. Here, we purified the 30S subunits of E. coli cells under various Mg2+ concentrations and analyzed their structural distortion by cryo-electron microscopy. Upon systematically interrogating the structural heterogeneity within the 1 mM Mg2+ dataset, we observed 30S particles with different levels of structural distortion in the decoding center, h17, and the 30S head. Our model showed that, when the Mg2+ concentration decreases, the decoding center distorts, starting from h44 and followed by the shifting of h18 and h27, as well as the dissociation of ribosomal protein S12. Mg2+ deficiency also eliminates the interactions between h17, h10, h15, and S16, resulting in the movement of h17 towards the tip of h6. More flexible structures were observed in the 30S head and platform, showing high variability in these regions. In summary, the structures resolved here showed several prominent distortion events in the decoding center and h17. The requirement for Mg2+ in ribosomes suggests that the conformational changes reported here are likely shared due to a lack of cellular Mg2+ in all domains of life. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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Review

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26 pages, 9848 KiB  
Review
Emerging Quantitative Biochemical, Structural, and Biophysical Methods for Studying Ribosome and Protein–RNA Complex Assembly
by Kavan Gor and Olivier Duss
Biomolecules 2023, 13(5), 866; https://doi.org/10.3390/biom13050866 - 19 May 2023
Cited by 3 | Viewed by 2283
Abstract
Ribosome assembly is one of the most fundamental processes of gene expression and has served as a playground for investigating the molecular mechanisms of how protein–RNA complexes (RNPs) assemble. A bacterial ribosome is composed of around 50 ribosomal proteins, several of which are [...] Read more.
Ribosome assembly is one of the most fundamental processes of gene expression and has served as a playground for investigating the molecular mechanisms of how protein–RNA complexes (RNPs) assemble. A bacterial ribosome is composed of around 50 ribosomal proteins, several of which are co-transcriptionally assembled on a ~4500-nucleotide-long pre-rRNA transcript that is further processed and modified during transcription, the entire process taking around 2 min in vivo and being assisted by dozens of assembly factors. How this complex molecular process works so efficiently to produce an active ribosome has been investigated over decades, resulting in the development of a plethora of novel approaches that can also be used to study the assembly of other RNPs in prokaryotes and eukaryotes. Here, we review biochemical, structural, and biophysical methods that have been developed and integrated to provide a detailed and quantitative understanding of the complex and intricate molecular process of bacterial ribosome assembly. We also discuss emerging, cutting-edge approaches that could be used in the future to study how transcription, rRNA processing, cellular factors, and the native cellular environment shape ribosome assembly and RNP assembly at large. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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18 pages, 3411 KiB  
Review
Ribosomal Protein uS5 and Friends: Protein–Protein Interactions Involved in Ribosome Assembly and Beyond
by Anne-Marie Landry-Voyer, Zabih Mir Hassani, Mariano Avino and François Bachand
Biomolecules 2023, 13(5), 853; https://doi.org/10.3390/biom13050853 - 18 May 2023
Cited by 3 | Viewed by 1842
Abstract
Ribosomal proteins are fundamental components of the ribosomes in all living cells. The ribosomal protein uS5 (Rps2) is a stable component of the small ribosomal subunit within all three domains of life. In addition to its interactions with proximal ribosomal proteins and rRNA [...] Read more.
Ribosomal proteins are fundamental components of the ribosomes in all living cells. The ribosomal protein uS5 (Rps2) is a stable component of the small ribosomal subunit within all three domains of life. In addition to its interactions with proximal ribosomal proteins and rRNA inside the ribosome, uS5 has a surprisingly complex network of evolutionarily conserved non-ribosome-associated proteins. In this review, we focus on a set of four conserved uS5-associated proteins: the protein arginine methyltransferase 3 (PRMT3), the programmed cell death 2 (PDCD2) and its PDCD2-like (PDCD2L) paralog, and the zinc finger protein, ZNF277. We discuss recent work that presents PDCD2 and homologs as a dedicated uS5 chaperone and PDCD2L as a potential adaptor protein for the nuclear export of pre-40S subunits. Although the functional significance of the PRMT3–uS5 and ZNF277–uS5 interactions remain elusive, we reflect on the potential roles of uS5 arginine methylation by PRMT3 and on data indicating that ZNF277 and PRMT3 compete for uS5 binding. Together, these discussions highlight the complex and conserved regulatory network responsible for monitoring the availability and the folding of uS5 for the formation of 40S ribosomal subunits and/or the role of uS5 in potential extra-ribosomal functions. Full article
(This article belongs to the Special Issue Ribosomal Proteins in Ribosome Assembly)
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