Ribosome biogenesis in man: Current views on nucleolar structures and function

Schwarzacher, H. G.; Mosgoeller, Wilhelm

doi:10.1159/000056853

Cited by 38 publications

(16 citation statements)

References 58 publications

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“…The absence of association of L13a R68A and R59A-K60A-R61A mutants with ribosomes and rRNA described above could be due to (i) inability of the mutant proteins to directly associate with rRNA, and/or (ii) inability of the mutant proteins to reach the nucleolar compartment(s) where most of the ribosome assembly events take place in eukaryotes (21). To distinguish between these possibilities, we used immunofluorescence to monitor the intracellular distribution of L13a and determine whether mutations that affect ribosomal incorporation of the protein also affect its import into the nucleolus.…”

Section: Resultsmentioning

confidence: 97%

Insights into the Mechanism of Ribosomal Incorporation of Mammalian L13a Protein during Ribosome Biogenesis

Das

Basu

Biswas

et al. 2013

Molecular and Cellular Biology

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bIn contrast to prokaryotes, the precise mechanism of incorporation of ribosomal proteins into ribosomes in eukaryotes is not well understood. For the majority of eukaryotic ribosomal proteins, residues critical for rRNA binding, a key step in the hierarchical assembly of ribosomes, have not been well defined. In this study, we used the mammalian ribosomal protein L13a as a model to investigate the mechanism(s) underlying eukaryotic ribosomal protein incorporation into ribosomes. This work identified the arginine residue at position 68 of L13a as being essential for L13a binding to rRNA and incorporation into ribosomes. We also demonstrated that incorporation of L13a takes place during maturation of the 90S preribosome in the nucleolus, but that translocation of L13a into the nucleolus is not sufficient for its incorporation into ribosomes. Incorporation of L13a into the 90S preribosome was required for rRNA methylation within the 90S complex. However, mutations abolishing ribosomal incorporation of L13a did not affect its ability to be phosphorylated or its extraribosomal function in GAIT element-mediated translational silencing. These results provide new insights into the mechanism of ribosomal incorporation of L13a and will be useful in guiding future studies aimed at fully deciphering mammalian ribosome biogenesis. Ribosome biogenesis is an essential and highly complex process in all living organisms. Ribosomes are composed of numerous precisely assembled proteins and rRNA molecules; thus, they present a paradigm for RNA-protein recognition/binding and ribonucleoprotein (RNP) folding. In prokaryotes, the highly ordered process of ribosome assembly is relatively well defined and has been shown to involve orchestrated changes in rRNA conformation and protein binding steps (1). In contrast, very little is known about the mechanism of eukaryotic ribosome assembly. Despite the general similarity of eukaryotic and prokaryotic ribosomes, they differ substantially in their size, structure, and subunit compositions (including the numbers and sequences of proteins and rRNAs). Another key difference is that the process of maturation and assembly of eukaryotic ribosomes is a highly compartmentalized process which starts in the nucleolus and finishes in the cytoplasm (2). Factors that are not ribosome components but are involved in the ribosome maturation and assembly process also may differ between prokaryotes and eukaryotes. Production of eukaryotic ribosomes (including export from the nucleolus into the cytoplasm) requires highly synchronized synthesis of four rRNAs, about 80 ribosomal proteins, 150 proteins that serve as assembly factors, and 70 small nucleolar RNAs (snoRNAs) that direct modifications to rRNAs (3, 4). Advances in affinity purification methods using epitope-tagged proteins and mass spectrometry have allowed molecular characterization of several distinct RNP complexes corresponding to nucleolar preribosomes at different stages of assembly (5-7). However, this information was primarily derived from stud...

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Section: Resultsmentioning

confidence: 97%

Insights into the Mechanism of Ribosomal Incorporation of Mammalian L13a Protein during Ribosome Biogenesis

Das

Basu

Biswas

et al. 2013

Molecular and Cellular Biology

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“…These include fibrillar centres (FCs), which are surrounded by dense fibrillar components (DFCs), and the FC-DFC complexes are embedded in the granular component (GC). Immuno-EM experiments show that many nucleolar proteins accumulate in one or two of these subcompartments, suggesting they each have distinct protein compositions and functions (Schwarzacher and Mosgoeller, 2000). For example, the RNA polymerase I subunit RPA39 is predominantly localised in the FC, whereas fibrillarin, a protein that is involved in ribose 2′-O-methylation of rRNA, accumulates in the DFC, and nucleolar phosphoprotein B23 is found in the GC.…”

Section: Nucleolusmentioning

confidence: 99%

The nucleolus

Lam

Trinkle-Mulcahy

Lamond

2005

Journal of Cell Science

162

137

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“…Results of many studies conducted by various techniques have proved convincingly that morphological characteristics of nucleoli are associated with the most important molecular-genetic processes and are objective indicators of cell metabolism features (Scheer and Weisenberger, 1994;Shaw and Jordan, 1995;Schwarzacher and Mosgoeller, 2000). Such a relation is easily explicable because the nucleolus is the site of transcription of ribosomal DNA, processing of the rDNA transcripts and the formation of pre-ribosomal components.…”

Section: Cytotoxicitymentioning

confidence: 98%

Use of a complex approach for assessment of metamizole sodium and acetylsalicylic acid toxicity, genotoxicity and cytotoxicity

Arkhipchuk¹,

Гончарук²,

Chernykh³

et al. 2004

J of Applied Toxicology

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A complex approach based on the use of test organisms belonging to different systematic groups (plants, invertebrates and vertebrates), as well as the nucleolar biomarker and the micronucleus test on their cells, was applied to assess the toxicity, cytotoxicity and genotoxicity of two pharmaceutical substances (metamizole sodium and acetylsalicylic acid) applied at ic(50) concentrations for mammalian cells. The compound acetylsalicylic acid was evaluated at a concentration (1.6 x 10(3) mg l(-1)) that was non-toxic for bioassays based on fish (Carassius auratus gibelio) and hydra (Hydra attenuata) and acutely toxic for bioassays with ceriodaphnia (Ceriodaphnia affinis) and onion (Allium cepa). The metamizole sodium solution (6.25%) demonstrated acute toxicity for the whole set of test organisms. Both drugs, after their 30-360 min influence on the test organisms, first changed the nucleolar size in plant and animal cells (i.e. the transcriptional activity of ribosomal genes was affected most significantly). Moreover, the metamizole sodium solution caused nucleolar structural damage in 90% of hydra cells as early as after 30 min of exposure. The acetylsalicylic acid solution inhibited essentially the rate of cell division in the meristem of onion roots (the mitotic index decreased to 9.6 per thousand, as compared 51.7 per thousand for the control). The carp incubation and the onion germination in the acetylsalicylic acid solution showed a reproducible increase in the frequency of cells with micronuclei (2 and 5.5 times, respectively) and double nuclei (3 and 1.5 times, respectively). The approach described herein may be applied for obtaining rapid, cost-efficient and useful supplementary data on different types of toxicity for marketed drugs as well as for drugs under development.

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Ribosome biogenesis in man: Current views on nucleolar structures and function

Cited by 38 publications

References 58 publications

Insights into the Mechanism of Ribosomal Incorporation of Mammalian L13a Protein during Ribosome Biogenesis

Insights into the Mechanism of Ribosomal Incorporation of Mammalian L13a Protein during Ribosome Biogenesis

The nucleolus

Use of a complex approach for assessment of metamizole sodium and acetylsalicylic acid toxicity, genotoxicity and cytotoxicity

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