Nucleolus: Structure and Function

Mark OJ Olson, University of Mississippi Medical Center, Jackson, Mississippi, USA

Published online: December 2010

DOI: 10.1002/9780470015902.a0005975.pub2

The nucleolus is the nuclear subdomain that assembles ribosomal subunits in eukaryotic cells. The nucleolar organiser regions of chromosomes, which contain the genes for pre-ribosomal ribonucleic acid (rRNA), serve as the foundation for nucleolar structure. The nucleolus disassembles at the beginning of mitosis, its components disperse in various parts of the cell and reassembly occurs during telophase and early G1 phase. Ribosome assembly begins with transcription of pre-rRNA. During transcription ribosomal and nonribosomal proteins attach to the RNA. Subsequently, there is modification and cleavage of pre-rRNA and incorporation of more ribosomal proteins and 5S rRNA into maturing pre-ribosomal complexes. The nucleolus also contains proteins and RNAs that are not related to ribosome assembly and a number of new functions for the nucleolus have been identified. These include assembly of signal recognition particles, sensing cellular stress and transport of human immunodeficiency virus 1 (HIV-1) messenger RNA.

Key Concepts:

  • The nucleolus, whose primary function is to assemble ribosomes, is the largest structure in the cell nucleus.
  • The nucleolus organiser regions of chromosomes, which contain the genes for pre-rRNA, are the foundation for the nucleolus.
  • All active nucleoli contain at least two ultrastructural components, the nucleolar dense fibrillar component representing early pre-ribosomal complexes and the granular component containing more mature pre-ribosomal particles.
  • Most nucleoli in higher eukaryotes also contain fibrillar centres, which are the interphase equivalents of the nucleolus organiser regions.
  • The nucleolus disassembles at the beginning of mitosis and begins to reassemble in telophase.
  • Ribosome assembly begins with the transcription of pre-rRNA by RNA polymerase I.
  • Ribosomal and nonribosomal proteins and 5S RNA associate with the pre-rRNA during and after transcription.
  • The pre-rRNA is modified and processed into rRNA with the aid of nonribosomal proteins and small nucleolar RNAs.
  • The nucleolus has numerous other functions including assembly of signal recognition particles, modification of transfer RNAs and sensing cellular stress.

Keywords: nucleolus; ribosome biogenesis; pre-rRNA; RNA processing; SnoRNAs

Figure 1. Electron micrographs of nucleoli from human HeLa cells showing examples of two different types of subnucleolar organisation of the components in cell nucleoli. (a) Reticulated type of nucleolus, which is often found in transcriptionally active cells. These nucleoli have relatively small fibrillar centres (F) surrounded by strands of dense fibrillar component (D). The nucleolar interstices (I) appear as regions of lower electron density and contain a few strands of intranucleolar chromatin. The small punctate granular components (G) are scattered throughout the nucleolus. (b) More common form of structural organisation, in which the nucleoli have large and prominent fibrillar centres (F) surrounded by dense fibrillar components (D). Relatively large areas are covered by the granular components (G), which are more clearly separated from the dense fibrillar components than in reticulated nucleoli. In (b) a Cajal body (arrowheads) seems to be attached to the nucleolus through clumps of perinucleolar chromatin, which were detected by immunogold staining using an antibody against single-stranded DNA. Reproduced from Olson MOJ, Dundr M and Szebeni A (2000) The nucleolus: an old factory with unexpected capabilities. Trends in Cell Biology 10: 189–196, with permission from Elsevier. Scale bars, 200 nm.
Figure 2. Principal steps in vertebrate ribosome assembly. The process begins in the nucleolus with transcription of 47S pre-rRNA. During and after transcription, nonribosomal proteins and snoRNAs associate with the pre-rRNA transcript. Methylation and pseudouridylation of the nascent pre-rRNA is guided by the snoRNAs. 5S rRNA, which is synthesised in the nucleoplasm and ultimately becomes a component of the 60S subunit, is added to the maturing complex at an undefined stage. The pre-rRNA undergoes a series of cleavages that result ultimately in 18S, 5.8S and 28S rRNAs (see Figure 3). The complex is split into two precursor particles corresponding to the small (40S) and large (60S) ribosomal subunits. Ribosomal proteins are added to the precursor complexes at various stages of assembly. The nearly mature subunits are transported to the cytoplasm, where final maturation takes place and the small and large subunits are incorporated into ribosomes.
Figure 3. Features of pre-rRNA processing in vertebrates. The pathway shown is compiled from reviews by Eichler and Craig (1994) and Sollner-Webb et al. (1996). The sizes of the intermediates are those found in mouse; human cells follow a very similar but slightly different pathway. The 47S pre-rRNA transcript contains a 5¢ external transcribed spacer (5¢ ETS) region, two internal transcribed spacer (ITS1 and ITS2) segments and a 3¢ external transcribed spacer (3¢ ETS) region, all of which are removed to generate 18S, 5.8S and 28S rRNAs. The first processing event is indicated by the arrow near the 5¢ end of the 47S transcript. The mature rRNAs are produced by sequential endonuclease cleavage, with some of the mature rRNA termini generated by exonuclease digestion. The distribution of the mature rRNAs in the ribosomal subunits is shown below. The 5.8S rRNA is associated with the 5¢ end of 28S rRNA through hydrogen bonding. It associates with ribosomal protein L5 before being incorporated into the large ribosomal subunit.
Figure 4. Nontraditional roles of the nucleolus. Several examples are illustrated in the figure. A variety of cellular processes occur in the nucleolus including tRNA maturation and partial assembly of signal recognition particles (SRPs) and telomerase complexes. The yeast cell cycle is regulated through nucleolar sequestration of the cdc14p protein phosphatase in the RENT complex, which also contains the proteins Sir2p and Net1p. The activity of tumour-suppressor protein p53 is also regulated by sequestration in the nucleolus of components that control its degradation (MDM2 and E2F1), which bind to the ARF protein. The HIV-1 Rev protein interacts with protein B23 in the nucleolus and also recruits the nuclear export factor hCRM1 and nucleoporins Nup98 and Nup214 to the nucleolus. Proteins Sir3p and Sir4p relocate from telomeres to nucleoli during aging in yeast, presumably in response to accumulation of extrachromosomal circles of rDNA. Sir2p also participates in chromatin silencing and suppression of extrachromosomal circle formation. Reproduced from Olson et al. (2002), with permission from Elsevier.
Figure 5. The HIV-1 Rev protein accumulates in the nucleoli of HIV-1 infected cells. HeLa cells were transfected with the HIV-1 molecular clone PNL4-3, which expresses the Rev protein in a cascade of viral progression. Twenty-four hours after transfection the HIV-1 Rev protein detected by a specific antibody is localised predominantly in the nucleoli (green). Viral replication was monitored by an antibody against the HIV-1 p24-core protein (red). The overlay of all three labellings is shown in the lower right panel. Bar, 2 m. Reproduced from Olson (2005), with permission from Springer.
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 References
    Ahmad Y, Boisvert F-M, Gregor P, Cobley A and Lamond AI (2009) NOPdb: Nucleolar Proteome Database – 2008. Nucleic Acids Research 37: D181–D184.
    Boisvert F-M, van Koningsbruggen S, Navascues J and Lamond AI (2007) The multifunctional nucleolus. Nature Reviews of Molecular and Cellular Biology 8: 574–585.
    Chen C-L, Chen C-J, Vallon O et al. (2008) Genomewide analysis of box C/D and box H/ACA snoRNAs in Chlamydomonas reinhardtii reaveals an extensive organization into intronic gene clusters. Genetics 179: 21–30.
    Dai M-S, Sun X-X and Lu H (2008) Aberrant expression of nucleostemin activates p53 and induces cell cycle arrest via inhibition of MDM2. Molecular and Cellular Biology 28: 4365–4376.
    Dundr M, Misteli T and Olson MOJ (2000) The dynamics of postmitotic re-assembly of the nucleolus. Journal of Cell Biology 150: 443–446.
    Eichler DC and Craig N (1994) Processing of eukaryotic ribosomal RNA. Progress in Nucleic Acid Research and Molecular Biology 49: 197–239.
    Elicieri GL (1999) Small nucleolar RNAs. Cellular and Molecular Life Sciences 56: 22–31.
    book Hadjiolov AA (1985) The Nucleolus and Ribosome Biogenesis. Vienna: Springer.
    Kiss T, Fayet-Lebaron E and Jady BE (2010) Box H/ACA small ribonucleoproteins. Molecular Cell 37: 597–606.
    Lafontaine DL and Tollervey D (2001) The function and synthesis of ribosomes. Nature Reviews. Molecular Cell Biology 2: 514–520.
    Lindström M, Deisenroth C and Zhang Y (2007) Putting a finger on growth surveillance. Cell Cycle 6: 434–437.
    Lopez MD, Rosenblad MA and Samuelsson T (2009) Conserved and variable domains of RNase MRP RNA. RNA Biology 6: 208–220.
    book Lucchini R and Sogo JM (1998) "The dynamic structure of ribosomal RNA gene chromatin". In: Paule M (ed.) Transcription of Eukaryotic Ribosomal RNA Genes by RNA Polymerase I, pp. 255–276. New York: Springer.
    Michienzi A, De Angelis FG, Bozzoni I and Rossi JJ (2006) A nucleolar localizing Rev binding element inhibits HIV replication. AIDS Research and Therapy 3: 13.
    Mougey EB, O'Reilly M, Osheim Y et al. (1993) The terminal balls characteristic of eukaryotic rRNA transcription units in chromatin spreads are rRNA processing complexes. Genes & Development 7: 1609–1619.
    book Olson MOJ (ed.) (2004a) "Nontraditional roles of the nucleolus". In: The Nucleolus, pp. 329–342. Austin: Landes Bioscience.
    Olson MOJ (2004b) Sensing cellular stress: another new function for the nucleolus? Science STKE 2004: e10.
    book Olson MOJ (2004c) The Nucleolus. Austin: Landes Bioscience.
    Olson MOJ (2005) The moving parts of the nucleolus. Histochemistry and Cell Biology 123(3): 203–216.
    Olson MOJ, Hingorani K and Szebeni A (2002) International Review of Cytology 219: 199–266.
    Pederson T and Tsai RYL (2009) In search of nonribosomal nucleolar protein function and regulation. Journal of Cell Science 184: 771–776.
    book Raué HA (2004) "Pre-ribosomal RNA processing and assembly in Saccharomyces cerevisiae". In: Olson MOJ (ed.) The Nucleolus, pp. 199–222. Austin: Landes Bioscience.
    Rubbi CP and Milner J (2003) Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage. EMBO Journal 22: 6068–6077.
    Savino TM, Gebrane-Younes J, De Mey J, Sibarita JB and Hernandez-Verdun D (2001) Nucleolar assembly of the rRNA processing machinery in living cells. Journal of Cell Biology 153: 1097–1110.
    Sirri V, Urcuqui-Inchima S, Roussel P and Hernandez-Verdun D (2008) Nucleolus: the fascinating nuclear body. Histochemistry and Cell Biology 129: 13–31.
    book Sollner-Webb B, Tycowski KT and Steitz JA (1996) "Ribosomal RNA processing in eukaryotes". In: Zimmerman RA and Dahlberg AE (eds) Ribosomal RNA: Structure Evolution, Gene Expression and Function in Protein Synthesis, pp. 469–490. Boca Raton, FL: CRC Press.
    Stark LA and Taliansky M (2009) Old and new faces of the nucleolus. EMBO Reports 10: 35–40.
    book Thiry M and Goessens G (1996) The Nucleolus during the Cell Cycle. Austin, TX: RG Landes.
    Thiry M and Lafontaine DL (2005) Birth of a nucleolus: the evolution of nucleolar compartments. Trends in Cell Biology 15: 194–199.
    Trinkle-Mulcahy L and Lamond AI (2006) Mitotic phosphatises: no longer silent partners. Current Opinion in Cell Biology 18: 623–631.
    Tsai RYL and McKay RDG (2005) A multistep, GTP-driven mechanism controlling the dynamic cycling of nucleostemin. Journal of Cell Science 168: 179–184.
    Weinstein LB and Steitz JA (1999) Guided tours: from precursor snoRNA to functional snoRNP. Current Opinion in Cell Biology 11: 378–384.
 Further Reading
    book Busch H and Smetana K (1970) The Nucleolus. New York: Academic Press.
    Carmo-Fonseca M, Mendes-Soares L and Campos I (2000) To be or not to be in the nucleolus. Nature Cell Biology 2: E107–E112.
    Grummt I (1999) Regulation of mammalian ribosomal gene transcription by RNA polymerase I. Progress in Nucleic Acid Research and Molecular Biology 62: 109–154.
    Henras AK, Soudet J and Gérus M (2008) The post-transcriptional steps of eukaryotic ribosome biogenesis. Cellular and Molecular Life Sciences 65: 2334–2359.
    book Paule M (1998) Transcription of Eukaryotic ribosomal RNA Genes by RNA polymerase I. New York: Springer.
    Politz JC, Yarovoi S, Kilroy SM et al. (2000) Signal recognition particle components in the nucleolus. Proceedings of the National Academy of Sciences of the USA 97: 55–60.
    Scheer U and Hock R (1999) Structure and function of the nucleolus. Current Opinion in Cell Biology 11: 385–390.
    Wolin SL and Matera AG (1999) The trials and travels of tRNA. Genes & Development 13: 1–10.

Related Sub-Topics:

Basic Cell Biology, Protein, RNA and DNA | Cell Compartments and Cellular Organelles | Growth and Synthesis | Nucleic Acid Structure | Transcription | Transcription of DNA | RNA Structure and Function | Posttranscriptional Modification
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Article Title: Nucleolus: Structure and Function
 
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Olson, Mark OJ(Dec 2010) Nucleolus: Structure and Function. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005975.pub2]