The Nucleolus and Ribosome Biogenesis

The nucleolus had consistently attracted the attention of investigators in the fields of cell biology and pathology. Because of its ubiquitous presence in the nucleus of eukaryotic cells, its rapid changes during their life cycle, and its rapid response to noxious agents, this organelle has been the subject of a large number of studies. Yet, the exact function and the very reason for the existence of the nucleolus (the only large cellular structure not delimited by a membrane) remain largely unknown. The ribosomes were discovered relatively late in the study of cells, but due to their crucial involvement in the protein synthesis machinery of all living organisms, the elucidation of their structure and function quickly became one of the major goals of molecular biology. The relatively simple structure of the ribosome strengthens the hope that a full understanding of the structure and function of this organelle in molecular terms is within the reach of contemporary research~ Since each of the rRNA and protein molecules embodied in the ribosome is the product of a distinct gene, studies on the biogenesis of ribosomes expanded rapidly to become a core topic in molecular genetics.

I. Introduction.- II. Ribosomal Genes.- II. 1. Definitions.- II.2. Ribosomal RNA Genes.- II.2.1. Multiplicity.- II.2.2. Chromosomal Location.- II.2.3. Extrachromosomal rRNA Genes.- II.2.4. Organization and Structure.- II.2.4.1. Saccharomyces cerevisiae.- II.2.4.2. Tetrahymena.- II.2.4.3. Drosophila.- II.2.4.4. Xenopus laevis.- II.2.4.5. Higher Plants.- II.2.4.6. Mammalia.- II.2.5. General Features.- II.3. 5 S rRNA Genes.- II.3.1. Number and Chromosomal Location.- II.3.2. Organization and Structure.- II.4. Ribosomal Protein Genes.- II.5. Synopsis.- III. Transcription of Ribosomal Genes.- III. 1. Components of the Transcription Complex.- III. 1.1. RNA Polymerases.- III. 1.2. Nucleolar rDNA and r-Chromatin.- III.2. The Transcription Process >.- III.2.1. Topology of Primary Pre-rRNA.- III.2.2. Morphology of Transcribed rRNA Genes.- III.2.3. Transcribed and Non-Transcribed r-Chromatin.- III.2.4. Primary Transcripts and Primary Pre-rRNA.- III.2.5. Transcription Initiation and Termination.- III.2.5.1. Initiation.- III.2.5.2. Termination.- III.2.6. Transcription in vitro.- III.3. Transcription of 5 S rRNA Genes.- III.4. Transcription of r-Protein Genes.- III.5. Synopsis.- IV. Maturation of Preribosomes.- IV. 1. Structure of Primary Pre-rRNA.- IV. 1.1. Size and Primary Structure.- IV. 1.2. Modifications.- IV. 1.3. Conformation.- IV.2. Pre-rRNA Maturation Pathways.- IV.2.1. General Considerations.- IV.2.2. Common Pattern of Pre-rRNA Maturation.- IV.2.3. Multiplicity of Maturation Pathways.- IV. 2.4. Enzyme Mechanisms.- IV. 3. Preribosomes: Structure and Maturation.- IV. 4. Synopsis.- V. Molecular Architecture of the Nucleolus.- V. 1. Introduction.- V.2. Nucleolus Organizer.- V. 2.1. Chromosomes.- V.2.2. Interphase Nuclei.- V.3. Fibrillar and Granular Components.- V.3.1. The Fibrillar Component.- V.3.2. The Granular Component.- V.4. The Nucleolus and Other Nuclear Structures.- V.4.1. Nucleolus-Associated Chromatin.- V.4.2. The Junction with the Nuclear Envelope.- V.5. The Nucleolar Matrix.- V.6. Macromolecular Constituents.- V.6.1. DNA and RNA.- V. 6.2. Nucleolar Proteins.- V.6.2.1. General.- V.6.2.2. Ag-NOR Protein(s).- V. 6.2.3. Nucleolar Antigens.- V. 7. Outline.- VI. Regulation.- VI. l. General Considerations.- VI.2. Transscriptional Control.- VI. 2.1. Transitions in the State of Expression of rRNA Genes.- VI. 2.1.1. Inactive r-Chromatin.- VI.2.1.2. Potentialy Active and Transcribed rRNA Genes.- VI.2.2. Control of Transcription Rate.- VI.2.2.1. Role of RNA Polymerase I.- VI.2.2.2. Supply of Nucleoside-5’-Triphosphates….- VI.2.2.3. Role of Protein Synthesis.- VI.3. Posttranscriptional Control.- VI.3.1. Synthesis and Supply of r-Proteins.- VI.3.2. The Role of Pre-rRNA Structure.- VI.3.3. The Role of 5 S rRNA.- VI.3.4. Critical Control Sites.- VI.3.4.1. Alternative Processing Pathways and Intranuclear Degradation of Preribosomes and Ribosomes.- VI.3.4.2. Release From the Nucleolus and Nucleo- Cytoplasmic Transport of Ribosomes.- VI.3.4.3. Turnover of Ribosomes.- VI.4. Autogeneous Regulation of Ribosome Biogenesis in Eukaryotes: A Model.- VI.5. Synopsis.- VII. Ribosome Biogenesis in the Life Cycle of Normal and Cancer Cells.- VII. 1. Nucleologenesis and Nucleololysis.- VII. 1.1. Nucleoli and Ribosome Biogenesis Düring the Mitotic Cycle.- VII. 1.2. Nucleologenesis.- VII. 1.3. Nuclyeololysis.- VII.2. Inhibition of Ribosome Biogenesis.- VII.2.1. Inhibitors Interacting With DNA and Chromatin.- VII.2.2. Inhibitors That Act on RNA Polymerases.- VII.2.3. Inhibitors of Nucleoside-5’-Triphosphate Formation.- VII.2.4. The Effects of Analogues Incorporated into Polyribonu- cleotide Chains.- VII.2.5. Inhibitors of Protein Synthesis.- VII.2.6. Interpretation of Nucleolar Alterations.- VII.2.6.1. Nucleolar Segregation.- VII.2.6.2. Nucleolar Spherical Bodies and Perichromatin Granules.- VII.2.6.3. Microspherules.- VII.2.6.4. Nucleolar Fragmentation.- VII.3. Growth Transitions.- VII.3.1. Modulation of Growth Rates in Yeasts.- VII.3.2. Activation of Lymphocytes.- VII.3.3. Growth Stimulation of Cultured Cells.- VII.3.4. Differentiation of Myoblasts in Culture.- VII.3.5. Regeneration of Rat Liver.- VII.4. Senescent and Cancer Cells.- VII.4.1. Senscent Cells and Tissues.- VII.4.2. Cancer Cells.- VII.5. Synopsis.- References.