scholarly journals The Nucleolus ofCaenorhabditis elegans

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Li-Wei Lee ◽  
Chi-Chang Lee ◽  
Chi-Ruei Huang ◽  
Szecheng J. Lo
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Size Control ◽  
Cell Types ◽  
C Elegans ◽  
Homologous Genes ◽  
Early Embryos ◽  
Human Disorders ◽  
Nucleolar Size

Nucleolar size and appearance correlate with ribosome biogenesis and cellular activity. The mechanisms underlying changes in nucleolar appearance and regulation of nucleolar size that occur during differentiation and cell cycle progression are not well understood.Caenorhabditis elegansprovides a good model for studying these processes because of its small size and transparent body, well-characterized cell types and lineages, and because its cells display various sizes of nucleoli. This paper details the advantages of usingC. elegansto investigate features of the nucleolus during the organism's development by following dynamic changes in fibrillarin (FIB-1) in the cells of early embryos and aged worms. This paper also illustrates the involvement of thencl-1gene and other possible candidate genes in nucleolar-size control. Lastly, we summarize the ribosomal proteins involved in life span and innate immunity, and those homologous genes that correspond to human disorders of ribosomopathy.

scholarly journals Repressed synthesis of ribosomal proteins generates protein-specific cell cycle and morphological phenotypes

2013 ◽  
Vol 24 (23) ◽  
pp. 3620-3633 ◽  
Author(s):  
Mamata Thapa ◽  
Ananth Bommakanti ◽  
Md. Shamsuzzaman ◽  
Brian Gregory ◽  
Leigh Samsel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Physical Structure ◽  
Specific Cell ◽  
M Cell ◽  
Cycle Progression ◽  
M Phase

The biogenesis of ribosomes is coordinated with cell growth and proliferation. Distortion of the coordinated synthesis of ribosomal components affects not only ribosome formation, but also cell fate. However, the connection between ribosome biogenesis and cell fate is not well understood. To establish a model system for inquiries into these processes, we systematically analyzed cell cycle progression, cell morphology, and bud site selection after repression of 54 individual ribosomal protein (r-protein) genes in Saccharomyces cerevisiae. We found that repression of nine 60S r-protein genes results in arrest in the G2/M phase, whereas repression of nine other 60S and 22 40S r-protein genes causes arrest in the G1 phase. Furthermore, bud morphology changes after repression of some r-protein genes. For example, very elongated buds form after repression of seven 60S r-protein genes. These genes overlap with, but are not identical to, those causing the G2/M cell cycle phenotype. Finally, repression of most r-protein genes results in changed sites of bud formation. Strikingly, the r-proteins whose repression generates similar effects on cell cycle progression cluster in the ribosome physical structure, suggesting that different topological areas of the precursor and/or mature ribosome are mechanistically connected to separate aspects of the cell cycle.

scholarly journals Stable C. elegans chromatin domains separate broadly expressed and developmentally regulated genes

2016 ◽  
Author(s):  
Kenneth J. Evans ◽  
Ni Huang ◽  
Przemyslaw Stempor ◽  
Michael A. Chesney ◽  
Thomas A. Down ◽  
...  
Keyword(s):  
Domain Structure ◽  
Germ Line ◽  
Cell Types ◽  
Chromatin Domain ◽  
Developmentally Regulated ◽  
Chromatin Domains ◽  
Domain Organization ◽  
C Elegans ◽  
Border Regions ◽  
Early Embryos

AbstractEukaryotic genomes are organized into domains of differing structure and activity. There is evidence that the domain organization of the genome regulates its activity, yet our understanding of domain properties and the factors that influence their formation is poor. Here we use chromatin state analyses in early embryos and L3 larvae to investigate genome domain organization and its regulation in C. elegans. At both stages we find that the genome is organized into extended chromatin domains of high or low gene activity defined by different subsets of states, and enriched for H3K36me3 or H3K27me3 respectively. The border regions between domains contain large intergenic regions and a high density of transcription factor binding, suggesting a role for transcription regulation in separating chromatin domains. Despite the differences in cell types, overall domain organization is remarkably similar in early embryos and L3 larvae, with conservation of 85% of domain border positions. Most genes in high activity domains are expressed in the germ line and broadly across cell types, whereas low activity domains are enriched for genes that are developmentally regulated. We find that domains are regulated by the germ line H3K36 methyltransferase MES-4 and that border regions show striking remodeling of H3K27me1, supporting roles for H3K36 and H3K27 methylation in regulating domain structure. Our analyses of C. elegans chromatin domain structure show that genes are organized by type into domains that have differing modes of regulation.Significance statementGenomes are organized into domains of different structure and activity, yet our understanding of their formation and regulation is poor. We show that C. elegans chromatin domain organization in early embryos and L3 larvae is remarkably similar despite the two developmental stages containing very different cell types. Chromatin domains separate genes into those with stable versus developmentally regulated expression. Analyses of chromatin domain structure suggest that transcription regulation and germ line chromatin regulation play roles in separating chromatin domains. Our results further our understanding of genome domain organization.

scholarly journals Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

2021 ◽  
Vol 8 ◽  
Author(s):  
Irene Delgado-Román ◽  
Mari Cruz Muñoz-Centeno
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Mrna Translation ◽  
Rna Polymerases ◽  
Specific Cell ◽  
Cycle Progression ◽  
Nuclear Rna

Eukaryotic life is possible due to the multitude of complex and precise phenomena that take place in the cell. Essential processes like gene transcription, mRNA translation, cell growth, and proliferation, or membrane traffic, among many others, are strictly regulated to ensure functional success. Such systems or vital processes do not work and adjusts independently of each other. It is required to ensure coordination among them which requires communication, or crosstalk, between their different elements through the establishment of complex regulatory networks. Distortion of this coordination affects, not only the specific processes involved, but also the whole cell fate. However, the connection between some systems and cell fate, is not yet very well understood and opens lots of interesting questions. In this review, we focus on the coordination between the function of the three nuclear RNA polymerases and cell cycle progression. Although we mainly focus on the model organism Saccharomyces cerevisiae, different aspects and similarities in higher eukaryotes are also addressed. We will first focus on how the different phases of the cell cycle affect the RNA polymerases activity and then how RNA polymerases status impacts on cell cycle. A good example of how RNA polymerases functions impact on cell cycle is the ribosome biogenesis process, which needs the coordinated and balanced production of mRNAs and rRNAs synthesized by the three eukaryotic RNA polymerases. Distortions of this balance generates ribosome biogenesis alterations that can impact cell cycle progression. We also pay attention to those cases where specific cell cycle defects generate in response to repressed synthesis of ribosomal proteins or RNA polymerases assembly defects.

Ribosome Dysfunction and Ineffective Hematopoiesis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-11-SCI-11
Author(s):  
Benjamin L. Ebert
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Bone Marrow Failure ◽  
Ribosomal Genes ◽  
Limb Bud ◽  
Refractory Anemia ◽  
Diamond Blackfan Anemia ◽  
Rare Congenital Disorder ◽  
Human Disorders ◽  
And Function

Abstract Abstract SCI-11 The 5q- syndrome and Diamond Blackfan Anemia are related on a molecular level by ribosome dysfunction. The 5q- syndrome is a distinct subtype of myelodysplastic syndrome (MDS) associated with isolated, interstitial deletions of the long arm of Chromosome 5. Diamond Blackfan Anemia is a rare congenital disorder associated with bone marrow failure, craniofacial abnormalities, and limb bud defects. The hematologic phenotype of both diseases includes a severe refractory anemia, macrocytosis, and a deficiency of erythroid precursors. Recent evidence indicates that this erythroid defect is caused by RPS14 deletion in the 5q- syndrome, and by mutation of RPS19 or other ribosomal genes in at least 50% of patients with Diamond Blackfan Anemia. In both diseases, deletion or mutation of one allele of a ribosomal protein leads to defects in pre-rRNA processing and defective production of mature ribosomes. In murine and zebrafish models, haploinsufficiency for ribosomal genes phenocopies the erythroid failure characteristic of the human disorders. While the mechanistic consequences of ribosomal dysfunction have not been fully elucidated, the p53 pathway appears to play a central role. MDM2, an E3 ubiquitin ligase that promotes the degradation of p53, binds to several ribosomal proteins including RPL11. Deficiency of RPS6, and perhaps other ribosomal proteins, causes an accumulation of free RPL11, that binds to MDM2, preventing MDM2 from interacting with p53, thereby leading to an accumulation of p53. Several other genes that are mutated in hematologic disorders are involved in ribosome biogenesis and function, including SBDS, mutated in Shwachman Diamond syndrome; DKC1, mutated in some cases of dyskaratosis congenita; and NPM1, mutated in acute myeloid leukemia and deleted in some cases of MDS. The manner in which each of these genes disrupt ribosome function and cause distinct clinical phenotypes is currently under investigation. Disclosures Ebert: GlaxoSmithKline: Research Funding.

scholarly journals SMK-1/PPH-4.1–mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos

2007 ◽  
Vol 179 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Seung-Hwan Kim ◽  
Antonia H. Holway ◽  
Suzanne Wolff ◽  
Andrew Dillin ◽  
W. Matthew Michael
Keyword(s):  
Dna Damage ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Germ Line ◽  
Embryonic Cell ◽  
Regulatory Subunit ◽  
Ataxia Telangiectasia Mutated ◽  
C Elegans ◽  
Early Embryos ◽  
Embryonic Cell Cycle

During early embryogenesis in Caenorhabditis elegans, the ATL-1–CHK-1 (ataxia telangiectasia mutated and Rad3 related–Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1–PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.

scholarly journals Ribosomopathies: New Therapeutic Perspectives

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2080
Author(s):  
Emilien Orgebin ◽  
François Lamoureux ◽  
Bertrand Isidor ◽  
Céline Charrier ◽  
Benjamin Ory ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Genetic Disorders ◽  
Cell Types ◽  
Treacher Collins Syndrome ◽  
Developmental Defects ◽  
Diamond Blackfan Anemia ◽  
New Therapeutic Approaches ◽  
Multiple Treatments ◽  
New Compounds

Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond–Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.

Red/green Dual Fluorescence Detection of Both the Nucleus and Nucleolus in Living Cells

2009 ◽  
Vol 17 (4) ◽  
pp. 18-21 ◽  
Author(s):  
Jack Coleman ◽  
Hilary Cox ◽  
Zaiguo Li ◽  
Praveen Pande ◽  
Dee Shen ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Dna And Rna ◽  
Nuclear Domain ◽  
Immunodeficiency Virus ◽  
Ribosomal Rna Processing ◽  
Hiv 1

The nucleolus represents a highly dynamic nuclear domain arising from an equilibrium between the level of ribosomal RNA synthesis and the efficiency of ribosomal RNA processing [1, 2]. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now demonstrate that it has additional functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response, and biogenesis of multiple ribonucleoprotein particles. Ribosome biogenesis is regulated throughout interphase and ceases during mitosis (Figure 1). Thus, there is a direct relationship between cell growth and nucleolar activities. Nucleoli are well known to be dramatically modified in cancer cells. Additionally, a large number of key proteins from both DNA- and RNA-containing viruses are localized in the nucleolus, including the human immunodeficiency virus (HIV)-1 Rev and Tat proteins. Targeting of viral proteins to the nucleolus not only facilitates virus replication, but may also be required for pathogenic processes. The nucleolus can also be considered a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm through its disruption.

scholarly journals Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Ribosome Biogenesis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Cellular Mechanisms ◽  
Cancerous Cell ◽  
First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

A Deficiency Screen for Zygotic Loci Required for Establishment and Patterning of the Epidermis in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 185-206 ◽  
Author(s):  
Rebecca M Terns ◽  
Peggy Kroll-Conner ◽  
Jiangwen Zhu ◽  
Sooyoun Chung ◽  
Joel H Rothman
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Epidermal Cells ◽  
Epidermal Differentiation ◽  
Apparent Effect ◽  
Internal Organs ◽  
C Elegans ◽  
Seam Cell ◽  
Genomic Regions ◽  
Caenorhabditis Elegans Genome

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least ∼67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

scholarly journals Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hauke S. Hillen ◽  
Elena Lavdovskaia ◽  
Franziska Nadler ◽  
Elisa Hanitsch ◽  
Andreas Linden ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Structural Basis ◽  
Peptidyl Transferase ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Ribosome ◽  
In Vitro Reconstitution

AbstractRibosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

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