The nucleolus is a nuclear substructure where the genes for three of the four ribosomal ribonucleic acids (rRNAs) are transcribed and where ribosomal subunits are assembled. Although the nucleolus has been intensively studied for many years, recent progress has been very rapid. We are beginning to understand how the biochemical processes carried out in the nucleolus relate to the observable structure. Recent observations of nucleolar proteins in living cells have shown that the nucleolus and its components are highly dynamic and that the observed structure is a steady state resulting from the relative nucleolar residence times of the various molecular components. There is much evidence that the nucleolus is also involved in many other roles, particularly in the biogenesis of RNA (ribonucleic acid)‐containing complexes, in stress sensing and in the control of cellular activity and proliferation. There is considerable current interest in the nucleolus and ribosome biogenesis as targets for cancer therapy.

Key Concepts

  • The nucleolus is the clearest subnuclear structure in most eukaryotic cells and is the site of rDNA transcription and ribosome biosynthesis.
  • Most nucleoli show three types of substructural components in standard thin section transmission electron microscopy: fibrillar centres (FC), dense fibrillar component (DFC) and granular component (GC).
  • The interpretation of nucleolar ultrastructure in functional terms is still not fully understood, but rDNA transcription occurs within the DFC, and the subsequent stages of rRNA processing occur vectorially in enveloping layers as the transcripts move away from the transcription sites.
  • Nucleoli share factors and, possibly, processes with other subnuclear structures, particularly Cajal bodies.
  • Most nucleolar proteins are highly dynamic and diffuse freely through the nucleolus and nucleoplasm; ‘nucleolar’ proteins have a longer residence time in the nucleolus than in other parts of the nucleus, but these nucleolar residence times are in some cases as short as a few tens of seconds.
  • The nucleolus is involved in many other nonconventional activities such as biogenesis of other RNP complexes, mRNA surveillance, and control of cell proliferation.
  • The nucleolus is involved in stress sensing and has roles in triggering the p53 DNA damage response pathways.

Keywords: ribosomal RNA; RNA polymerase I; nucleolar organisation; ribosome biosynthesis

Figure 1. The nucleolus as visualised by optical microscopy. (a) Isolated tobacco nuclei visualised by differential interference contrast microscopy. The nucleoli are clearly seen as prominent bodies inside each nucleus (No). Within many nucleoli, nucleolar vacuoles or cavities can be seen (NV). (b) Pea root tissue stained with the DNA dye 4′,6‐diamidino‐2‐phenylindole (DAPI) and imaged by confocal microscopy. The nuclear chromatin is brightly stained, whereas the nucleoli are visible as dark unstained regions within the nuclei (No). The nucleolus begins to break down during prophase (P) and disappears during mitosis. A cell at anaphase (A) is present in this micrograph.
Figure 2. Miller spread of ribosomal DNA (rDNA) transcription units (Christmas trees), redrawn from an original micrograph. (a) Diagram of the organisation of a single repeat unit of the rDNA. (b) Diagram of the initial pre‐rRNA 45S transcript and its processing pathway to three of the mature rRNAs. 1, internal transcribed spacer 1; 2, internal transcribed spacer 2; ETS, external transcribed spacer; NTS, nontranscribed spacer and the three mature rRNAs encoded by the rDNA are 18S, 5.8S and 28S.
Figure 3. Diagrams of nucleolar ultrastructure seen by conventional electron microscopy. (a)–(c) Nucleoli from a mammalian cell culture under different growth conditions. (a) Three well‐differentiated types of structure can be seen; lightly staining fibrillar centres (yellow), surrounded by regions of dense fibrillar component (darker blue). Most of the volume of the nucleolus is filled with particles – the granular component (lighter blue). (b) In a cell undergoing rapid growth and division, the nucleolus is often irregular and reticulated or stranded in appearance. (c) In arrested or inactive cells, or cells where transcription has been inhibited by drug treatment, the three components can become segregated into large blocks. (d) In a typical plant cell nucleolus, the DFC occupies a much larger proportion of the nucleolus and can often only be distinguished from the granular component by a different texture. Fibrillar centres are usually small and dispersed throughout the DFC, and there is often a central nucleolar cavity or vacuole.
Figure 4. Different views of nucleolar organisation. A typical plant nucleolus is illustrated diagrammatically. To give a common reference structure, an outline corresponding to the nucleolar region labelled by a probe to the external transcribed spacer (ETS) portion of the pre‐rRNA is shown. This corresponds to most, but not quite all, of the DFC. (a) Possible model for the organisation of rDNA transcription units within the nucleolus. RNP, ribonuclear particle. (b) Nucleolar structure seen by conventional thin‐section EM. DFC, dense fibrillar component; FC, fibrillar centre and GC, granular component. (c) Organisation of transcription sites and zones of transcript processing. ITS1, internal transcribed spacer 1. (d) Localisation of some nucleolar proteins and small nucleolar RNAs.


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Shaw, Peter J(Nov 2015) Nucleolus. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001352.pub4]