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Nuclear speckles: a model for nuclear organelles

Nature Reviews Molecular Cell Biology volume 4, pages 605–612 (2003)Cite this article

Key Points

  • Speckles are dynamic subnuclear structures that contain pre-messenger RNA splicing factors and other proteins that are involved in transcription, 3′- end RNA-processing and reversible protein phosphorylation. The formation of speckles is regulated during the cell-division cycle.

  • Splicing factors cycle continually between speckles and the nucleoplasm. Their size and shape results from the dynamic exchange of factors into and out of speckles.

  • A reversible protein phosphorylation mechanism can regulate the movement of speckle components between speckles and other nuclear structures. It is likely that protein–protein interactions are primarily responsible for the formation and integrity of speckles.

  • Speckles contain little or no DNA and are not principal sites of transcription. Instead, they function as assembly/modification sites that can supply active splicing factors to sites of transcription.

  • We propose a 'regulated-exchange' model to account for the steady-state level of proteins in speckles. This envisages that the concentration of factors that are localized in speckles results from a regulated and cell-type-specific basal exchange rate of speckle components.

Abstract

Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. At the fluorescence-microscope level they appear as irregular, punctate structures, which vary in size and shape, and when examined by electron microscopy they are seen as clusters of interchromatin granules. Speckles are dynamic structures, and both their protein and RNA–protein components can cycle continuously between speckles and other nuclear locations, including active transcription sites. Studies on the composition, structure and behaviour of speckles have provided a model for understanding the functional compartmentalization of the nucleus and the organization of the gene-expression machinery.

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Figure 1: Speckles form in the interchromatin space.
Figure 2: Immuno-electron microscopic localization of pre-mRNA splicing factors.
Figure 3: Modulation of transcription affects speckle organization.
Figure 4: The speckle cell cycle.
Figure 5: A 'regulated-exchange' model accounts for the dynamics of nuclear speckles.

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References

  1. Misteli, T. Protein dynamics: implications for nuclear architecture and gene expression. Science 291, 843–847 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Spector, D. L. Nuclear bodies. J. Cell Sci. 114, 2891–2893 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Lamond, A. I. & Earnshaw, W. C. Structure and function in the nucleus. Science 280, 547–553 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Wansink, D. G. et al. Fluorescent labeling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus. J. Cell Biol. 122, 283–293 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Phair, R. D. & Misteli, T. High mobility of proteins in the mammalian cell nucleus. Nature 404, 604–609 (2000). Photobleaching techniques show that many classes of proteins can move rapidly within the nucleus and that they can rapidly associate and dissociate with nuclear compartments.

    Article  CAS  PubMed  Google Scholar 

  6. Beck, J. S. Variations in the morphological patterns of "autoimmune" nuclear fluorescence. Lancet 1, 1203–1205 (1961).

    Article  CAS  PubMed  Google Scholar 

  7. Swift, H. Studies on nuclear fine structure. Brookhaven Symp. Biol. 12, 134–152 (1959).

    CAS  PubMed  Google Scholar 

  8. Perraud, M., Gioud, M. & Monier, J. C. Intranuclear structures of monkey kidney cells recognised by immunofluorescence and immuno-electron microscopy using anti-ribonucleoprotein antibodies. Ann. Immunol. 130, 635–647 (1979) (in French).

    Google Scholar 

  9. Lerner, E. A., Lerner, M. R., Janeway, C. A. & Steitz, J. A. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc. Natl Acad. Sci. USA 78, 2737–2741 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Spector, D. L., Schrier, W. H. & Busch, H. Immunoelectron microscopic localization of snRNPs Biol. Cell 49, 1–10 (1983).

    Article  CAS  PubMed  Google Scholar 

  11. Thiry, M. The interchromatin granules. Histol. Histopathol. 10, 1035–1045 (1995).

    CAS  PubMed  Google Scholar 

  12. Wei, X., Somanathan, S., Samarabandu, J. & Berezney, R. Three-dimensional visualization of transcription sites and their association with splicing factor-rich nuclear speckles. J. Cell Biol. 146, 543–558 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Visa, N., Puvion-Dutilleul, F., Bachellerie, J. P. & Puvion, E. Intranuclear distribution of U1 and U2 snRNAs visualized by high resolution in situ hybridization: revelation of a novel compartment containing U1 but not U2 snRNA in HeLa cells. Eur. J. Cell Biol. 60, 308–321 (1993).

    CAS  PubMed  Google Scholar 

  14. Spector, D. L. Macromolecular domains within the cell nucleus. Annu. Rev. Cell Biol. 9, 265–315 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Fakan, S. Perichromatin fibrils are in situ forms of nascent transcripts. Trends Cell Biol. 4, 86–90 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Li, H. & Bingham, P. M. Arginine/serine-rich domains of the su(wa) and tra RNA processing regulators target proteins to a subnuclear compartment implicated in splicing. Cell 67, 335–342 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Hedley, M. L., Amrein, H. & Maniatis, T. An amino acid sequence motif sufficient for subnuclear localization of an arginine/serine rich splicing factor. Proc. Natl Acad. Sci. USA 92, 11524–11528 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Caceres, J. F., Misteli, T., Screaton, G. R., Spector, D. L. & Krainer, A. R. Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity. J. Cell Biol. 138, 225–238 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gall, J. G., Bellini, M., Wu, Z. & Murphy, C. Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes. Mol. Biol. Cell 10, 4385–4402 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Segalat, L. & Lepesant, J. A. Spatial distribution of the Sm antigen in Drosophila early embryos. Biol. Cell 75, 181–185 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Potashkin, J. A., Derby, R. J. & Spector, D. L. Differential distribution of factors involved in pre-mRNA processing in the yeast cell nucleus. Mol. Cell. Biochem. 10, 3524–3534 (1990).

    CAS  Google Scholar 

  22. Fox, A. H. et al. Paraspeckles: a novel nuclear domain. Curr. Biol. 12, 13–25 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Huang, S. & Spector, D. L. Nascent pre-mRNA transcripts are associated with nuclear regions enriched in splicing factors. Genes Dev. 5, 2288–2302 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Xing, Y., Johnson, C. V., Dobner, P. R. & Lawrence, J. B. Higher level organization of individual gene transcription and RNA splicing. Science 259, 1326–1330 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Xing, Y., Johnson, C. V., Moen, P. T., McNeil, J. A. & Lawrence, J. B. Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC35 domains. J. Cell Biol. 131, 1635–1647 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Smith, K. P., Moen, P. T., Wydner, K. L., Coleman, J. R. & Lawrence, J. B. Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific. J. Cell Biol. 144, 617–629 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Johnson, C. et al. Tracking COL1A1 RNA in osteogenesis imperfecta. Splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain. J. Cell Biol. 150, 417–432 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Misteli, T., Cáceres, J. F. & Spector, D. L. The dynamics of a pre-mRNA splicing factor in living cells. Nature 387, 523–527 (1997). The first study to show that speckles are dynamic structures that respond to activation of nearby genes, by using live imaging of cells expressing a fluorescent-protein-tagged splicing factor.

    Article  CAS  PubMed  Google Scholar 

  29. O'Keefe, R. T., Mayeda, A., Sadowski, C. L., Krainer, A. R. & Spector, D. L. Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors. J. Cell Biol. 124, 249–260 (1994).

    Article  CAS  PubMed  Google Scholar 

  30. Monneron, A. & Bernhard, W. Fine structural organization of the interphase nucleus in some mammalian cells. J. Ultrastruct. Res. 27, 266–288 (1969).

    Article  CAS  PubMed  Google Scholar 

  31. Fakan, S. & Bernhard, W. Localisation of rapidly and slowly labelled nuclear RNA as visualized by high resolution autoradiography. Exp. Cell Res. 67, 129–141 (1971).

    Article  CAS  PubMed  Google Scholar 

  32. Fakan, S. & Nobis, P. Ultrastructural localization of transcription sites and of RNA distribution during the cell cycle of synchronized CHO cells. Exp. Cell Res. 113, 327–337 (1978).

    Article  CAS  PubMed  Google Scholar 

  33. Cmarko, D. et al. Ultrastructural analysis of transcription and splicing in the cell nucleus after bromo-UTP microinjection. Mol. Biol. Cell 10, 211–223 (1999). This study showed that transcription is associated with perichromatin fibrils and not with nuclear speckles (IGCs).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Huang, S. & Spector, D. L. Intron-dependent recruitment of pre-mRNA splicing factors to sites of transcription. J. Cell Biol. 131, 719–732 (1996).

    Article  Google Scholar 

  35. Melcak, I. et al. Nuclear pre-mRNA compartmentalization: trafficking of released transcripts to splicing factor reservoirs. Mol. Biol. Cell 11, 497–510 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shopland, L. S., Johnson, C. V. & Lawrence, J. B. Evidence that all SC35 domains contain mRNAs and that transcripts can be structurally constrained within these domains. J. Struct. Biol. 140, 131–139 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Fu, X. -D. The superfamily of arginine/serine-rich splicing factors. RNA 1, 663–680 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Huang, S. & Spector, D. L. in Eukaryotic mRNA Processing (ed. Krainer, A. R.) 37–67 (Oxford Univ. Press, New York, 1997).

    Google Scholar 

  39. Colwill, K. et al. The Clk/Sty protein kinase phosphorylates splicing factors and regulates their intranuclear distribution. EMBO J. 15, 265–275 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ko, T. K., Kelly, E. & Pines, J. CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles. J. Cell Sci. 114, 2591–2603 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Kojima, T., Zama, T., Wada, K., Onogi, H. & Hagiwara, M. Cloning of human PRP4 reveals interaction with Clk1. J. Biol. Chem. 276, 32247–32256 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Sacco-Bubulya, P. & Spector, D. L. Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing. J. Cell Biol. 156, 425–436 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Brede, G., Solheim, J. & Prydz, H. PSKH1, a novel splice factor compartment-associated serine kinase. Nucleic Acids Res. 30, 5301–5309 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Trinkle-Mulcahy, L. et al. Nuclear organisation of NIPP1, a regulatory subunit of protein phosphatase 1 that associates with pre-mRNA splicing factors. J. Cell Sci. 112, 157–168 (1999).

    Article  CAS  PubMed  Google Scholar 

  45. Trinkle-Mulcahy, L., Sleeman, J. E. & Lamond, A. I. Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells. J. Cell Sci. 114, 4219–4228 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Misteli, T. & Spector, D. L. Protein phosphorylation and the nuclear organization of pre-mRNA splicing. Trends Cell Biol. 7, 135–138 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Mintz, P. J., Patterson, S. D., Neuwald, A. F., Spahr, C. S. & Spector, D. L. Purification and biochemical characterization of interchromatin granule clusters. EMBO J. 18, 4308–4320 (1999). The first systematic proteomic study of the protein components of nuclear speckles (IGCs), which were isolated from mouse liver nuclei.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Larsson, S. H. et al. Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. Cell 81, 391–401 (1995).

    Article  CAS  PubMed  Google Scholar 

  49. Mortillaro, M. J. et al. A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix. Proc. Natl Acad. Sci. USA 93, 8253–8257 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zeng, C., Kim, E., Warren, S. L. & Berget, S. M. Dynamic relocation of transcription and splicing factors dependent upon transcriptional activity. EMBO J. 16, 1401–1412 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Krause, S., Fakan, S., Weis, K. & Wahle, E. Immunodetection of poly(A) binding protein II in the cell nucleus. Exp. Cell Res. 214, 75–82 (1994).

    Article  CAS  PubMed  Google Scholar 

  52. Schul, W., van Driel, R. & de Jong, L. A subset of poly(A) polymerase is concentrated at sites of RNA synthesis and is associated with domains enriched in splicing factors and poly(A) RNA. Exp. Cell Res. 238, 1–12 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Dostie, J., Lejbkowicz, F. & Sonenberg, N. Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles. J. Cell Biol. 148, 239–247 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Li, Q. et al. Eukaryotic translation initiation factor 4AIII (eIF4AIII) is functionally distinct from eIF4AI and eIF4AII. Mol. Cell. Biol. 19, 7336–7346 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nakayasu, H. & Ueda, K. Small nuclear RNA–protein complex anchors on the actin filaments in bovine lymphocyte nuclear matrix. Cell Struct. Funct. 9, 317–325 (1984).

    Article  CAS  PubMed  Google Scholar 

  56. Jagatheesan, G. et al. Colocalization of intranuclear lamin foci with RNA splicing factors. J. Cell Sci. 112, 4651–4661 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Rappsilber, J., Ryder, U., Lamond, A. I. & Mann, M. Large-scale proteomic analysis of the human spliceosome. Genome Res. 12, 1231–1245 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhou, Z., Licklider, L. J., Gygi, S. P. & Reed, R. Comprehensive proteomic analysis of the human spliceosome. Nature 419, 182–185 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Bregman, D. B., Du, L., van der Zee, S. & Warren, S. L. Transcription-dependent redistribution of the large subunit of RNA polymerase II to discrete nuclear domains. J. Cell Biol. 129, 287–298 (1995).

    Article  CAS  PubMed  Google Scholar 

  60. Grande, M. A., van der Kraan, I., de Jong, L. & van Driel, R. Nuclear distribution of transcription factors in relation to sites of transcription and RNA polymerase II. J. Cell Sci. 110, 1781–1791 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Kimura, H., Sugaya, K. & Cook, P. R. The transcription cycle of RNA polymerase II in living cells. J. Cell Biol. 159, 777–782 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Doyle, O., Corden, J. L., Murphy, C. & Gall, J. G. The distribution of RNA polymerase II largest subunit (RPB1) in the Xenopus germinal vesicle. J. Struct. Biol. 140, 154–166 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. Price, D. H. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol. Cell. Biol. 20, 2629–2634 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Herrmann, C. H. & Mancini, M. A. The Cdk9 and cyclin T subunits of TAK/P-TEFb localize to splicing factor-rich nuclear speckle regions. J. Cell Sci. 114, 1491–1503 (2001).

    Article  CAS  PubMed  Google Scholar 

  65. Matera, A. G. & Ward, D. C. Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. J. Cell Biol. 121, 715–727 (1993).

    Article  CAS  PubMed  Google Scholar 

  66. Pessler, F., Pendergrast, P. S. & Hernandez, N. Purification and characterization of FBI-1, a cellular factor that binds to the human immunodeficiency virus type 1 inducer of short transcripts. Mol. Cell. Biol. 17, 3786–3798 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Pendergrast, P. S., Wang, C., Hernandez, N. & Huang, S. FBI-1 can stimulate HIV-1 Tat activity and is targeted to a novel subnuclear domain that includes the Tat-P-TEFb-containing nuclear speckles. Mol. Biol. Cell 13, 915–929 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hock, R., Wilde, F., Scheer, U. & Bustin, M. Dynamic relocation of chromosomal protein HMG-17 in the nucleus is dependent on transcriptional activity. EMBO J. 17, 6992–7001 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Carter, K. C., Taneja, K. L. & Lawrence, J. B. Discrete nuclear domains of poly(A) RNA and their relationship to the functional organization of the nucleus. J. Cell Biol. 115, 1191–1202 (1991).

    Article  CAS  PubMed  Google Scholar 

  70. Visa, N., Puvion-Dutilleul, F., Harper, F., Bachellerie, J. -P. & Puvion, E. Intranuclear distribution of poly A RNA determined by electron microscope in situ hybridization. Exp. Cell. Res. 208, 19–34 (1993).

    Article  CAS  PubMed  Google Scholar 

  71. Huang, S., Deerinck, M. H., Ellisman, M. H. & Spector, D. L. In vivo analysis of the stability and transport of nuclear poly(A)+ RNA. J. Cell Biol. 126, 877–899 (1994).

    Article  CAS  PubMed  Google Scholar 

  72. Erdmann, V. A., Szymanski, M., Hochberg, A., de Groot, N. & Barciszewski, J. Collection of mRNA-like non-coding RNAs. Nucleic Acids Res. 27, 192–195 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Herman, R. C., Williams, J. G. & Penman, S. Message and non-message sequences adjacent to poly(A) in steady state heterogeneous nuclear RNA of HeLa cells Cell 7, 429–437 (1976).

    Article  CAS  PubMed  Google Scholar 

  74. Zhao, K. et al. Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95, 625–636 (1998).

    Article  CAS  PubMed  Google Scholar 

  75. Boronenkov, I. V., Loijens, J. C., Umeda, M. & Anderson, R. A. Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol. Biol. Cell 9, 3547–3560 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Spann, T. P., Goldman, A. E., Wang, C., Huang, S. & Goldman, R. D. Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription. J. Cell Biol. 156, 603–608 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Spector, D. L., Fu, X. -D. & Maniatis, T. Associations between distinct pre-mRNA splicing components and the cell nucleus. EMBO J. 10, 3467–3481 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jiménez-García, L. F. & Spector, D. L. In vivo evidence that transcription and splicing are coordinated by a recruiting mechanism. Cell 73, 47–59 (1993). This work showed that factors are recruited from nuclear speckles to sites of transcription.

    Article  PubMed  Google Scholar 

  79. Bridge, E. et al. Dynamic organization of splicing factors in adenovirus-infected cells. J. Virol. 69, 281–290 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kruhlak, M. J. et al. Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state speckle compartments. J. Cell Biol. 150, 41–51 (2000). This study showed that the dynamics of splicing factor SF2/ASF are consistent with frequent but transient interactions with relatively immobile nuclear binding sites.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Spector, D. L. & Smith, H. C. Redistribution of U-snRNPs during mitosis. Exp. Cell Res. 163, 87–94 (1986).

    Article  CAS  PubMed  Google Scholar 

  82. Reuter, R., Appel, B., Rinke, J. & Lührmann, R. Localization and structure of snRNPs during mitosis. Immunofluorescent and biochemical studies. Exp. Cell Res. 159, 63–79 (1985).

    Article  CAS  PubMed  Google Scholar 

  83. Ferreira, J. A., Carmo-Fonseca, M. & Lamond, A. I. Differential interaction of splicing snRNPs with coiled bodies and interchromatin granules during mitosis and assembly of daughter cell nuclei. J. Cell Biol. 126, 11–23 (1994). This study identified MIGs as mitotic forms of speckles containing splicing factors and showed that interphase speckles can reform after mitosis, even in the absence of transcription.

    Article  CAS  PubMed  Google Scholar 

  84. Thiry, M. Behavior of interchromatin granules during the cell cycle Eur. J. Cell Biol. 68, 14–24 (1995). Analysis of the organization of IGCs through the cell cycle at the electron-microscope level.

    CAS  PubMed  Google Scholar 

  85. Leser, G. P., Fakan, S. & Martin, T. E. Ultrastructural distribution of ribonucleoprotein complexes duirng mitosis. snRNP antigens are contained in mitotic granule clusters. Eur. J. Cell Biol. 50, 376–389 (1989).

    CAS  PubMed  Google Scholar 

  86. Verheijen, R., Kuijpers, H., Vooijs, P., Van Venrooij, W. & Ramaekers, F. Distribution of the 70K U1 RNA-associated protein during interphase and mitosis. Correlation with other U RNP particles and proteins of the nuclear matrix. J. Cell Sci. 86, 173–190 (1986).

    Article  CAS  PubMed  Google Scholar 

  87. Prasanth, K. V., Sacco-Bubulya, P., Prasanth, S. G. & Spector, D. L. Sequential entry of components of gene expression machinery into daughter nuclei. Mol. Biol. Cell 14, 1043–1057 (2003). This study shows the differential timing of the re-entry of separate components of the gene-expression machinery into newly assembled daughter nuclei after mitosis. This re-entry occurs in a sequential and ordered manner.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Thiry, M. Differential location of nucleic acids within interchromatin granule clusters. Eur. J. Cell Biol. 62, 259–269 (1993).

    CAS  PubMed  Google Scholar 

  89. Misteli, T. & Spector, D. L. Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors. Mol. Biol. Cell 7, 1559–1572 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Spector, D. L., Lark, G. & Huang, S. Differences in snRNP localization between transformed and nontransformed cells. Mol. Biol. Cell 3, 555–569 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Spector, D. L., O'Keefe, R. T. & Jiménez-García, L. F. Dynamics of transcription and pre-mRNA splicing within the mammalian cell nucleus. Cold Spring Harb. Symp. Quant. Biol. 58, 799–805 (1993).

    Article  CAS  PubMed  Google Scholar 

  92. Gui, J. F., Lane, W. S. & Fu, X. -D. A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Nature 369, 678–682 (1994). Identifies and characterizes the role of a serine kinase, SRPK1, which phosphorylates SR proteins and modulates their localization during the cell cycle.

    Article  CAS  PubMed  Google Scholar 

  93. Gui, J. F., Tronchere, H., Chandler, S. D. & Fu, S. D. Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors. Proc. Natl Acad. Sci. USA 91, 10824–10828 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Misteli, T. et al. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. J. Cell Biol. 143, 297–307 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mermoud, J. E., Cohen, P. T. W. & Lamond, A. I. Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. EMBO J. 13, 5679–5688 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Turner, B. M. & Franchi, L. Identification of protein antigens associated with the nuclear matrix and with clusters of interchromatin granules in both interphase and mitotic cells. J. Cell Sci. 87, 269–282 (1987).

    Article  CAS  PubMed  Google Scholar 

  97. Pollard, T. D. & Earnshaw, W. C. Cell Biology (Saunders, Philadelphia, 2002).

    Google Scholar 

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Acknowledgements

We thank members of the Lamond group, and K.V. Prasanth and P. Sacco-Bubulya in the Spector group for their helpful comments. We also appreciate the comments of S. Fakan, J. Gall, G. Matera and J. Swedlow. We thank A. Fox and Y. Wah Lam (University of Dundee, UK) for their help in preparing figures 1 and 3, and P. Sacco-Bubulya (Cold Spring Harbor Laboratory) for providing figure 4. A. I. L. is a Wellcome Trust Principal Research Fellow. D. L. S. is funded by the National Institute of General Medical Sciences/ National Institutes of Health.

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Authors and Affiliations

  1. Wellcome Trust Biocentre, Medical Sciences Institute/Wellcome Trust Biocentre Complex, University of Dundee, Dundee, DD1 5EH, UK

    Angus I. Lamond

  2. Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, 11724, New York, USA

    David L. Spector

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DATABASES

Interpro

POZ-domain

Locus Link

PP1

PSP1

Swiss-Prot

Cdk9

cyclin-T1

CLK/STY

eIF4E

FBI-1

GFP

HMG-17

lamin A

PRP4

SRPK1

FURTHER INFORMATION

Angus I. Lamond's laboratory

David Spector's laboratory

Glossary

SPECKLE

An irregularly shaped nuclear domain that is visualized by immunofluorescence microscopy, typically by using anti-splicing-factor antibodies. Usually 25–50 speckles are observed per interphase mammalian nucleus.

PARASPECKLE

A subnuclear structure that is distinct from speckles. Typically, 10–20 paraspeckles are present in the interchromatin nucleoplasmic space, and they are often located adjacent to speckles. So far, three proteins — paraspeckle proteins 1 and 2 and p54/nrb — have been localized to these nuclear domains.

CAJAL BODY

A nuclear structure that contains newly assembled small nuclear ribonucleoprotein particles that are involved in pre-messenger RNA splicing, and small nucleolar ribonucleoprotein particles that are involved in ribosomal RNA processing. Also contains Cajal-body-specific guide RNAs. Cajal bodies are usually identified as foci labelled with antibodies against the autoantigen p80 coilin.

GEMS

'Gemini of Cajal bodies' are nuclear structures that are usually localized either coincident with or adjacent to Cajal bodies, depending on the cell line examined. Gems are characterized by the presence of the 'survival of motor neurons' (SMN) protein.

PROMYELOCYTIC LEUKAEMIA (PML) BODY

A subnuclear structure that is also known as nuclear domain 10, promyelocytic leukaemia oncogenic domain or Kr body. These bodies are characterized by the presence of the promyelocytic leukaemia protein and there are typically 10–30 per nucleus.

INTERCHROMATIN GRANULE CLUSTER

(IGC). A structure seen by electron microscopy that is equivalent to the speckles that are seen by fluorescence microscopy. Each IGC is composed of a series of particles, 20–25 nm in diameter, that seem to be connected in places by a thin fibril.

PERICHROMATIN FIBRILS

Fibrils observed by the electron microscope that are detected at transcription sites and shown to coincide with the incorporation of tritiated-uridine or 5-bromouridine 5′-trisphosphate, indicating that they are nascent transcripts.

INTERCHROMATIN-GRANULE-ASSOCIATED ZONE

A region that is adjacent to interchromatin granule clusters, which contains U1, but not U2, small nuclear RNAs.

SR PROTEINS

A family of pre-messenger RNA splicing factors that are characterized by repeats of arginine–serine dipeptides at their carboxyl termini.

SNURPOSOME

A nuclear structure, identified in amphibian oocytes, that contains splicing small nuclear ribonucleoprotein particles. Three classes — known as A, B and C snurposomes — have been defined, and they differ in their composition. B snurposomes are most closely related to speckles in their composition, and could represent oocyte forms of the speckles that are found in somatic-cell nuclei.

CELLULARIZATION

The transition from a syncytium to distinct cells which occurs at the fourteenth round of cell division in the Drosophila melanogaster embryo.

CLK/STY

A kinase family, the members of which are characterized by having the serine residues in the arginine–serine domain of SR proteins as their primary substrates.

PRP4

A kinase that localizes to nuclear speckles and interacts with CLK/STY, as well as several proteins that are involved in pre-mRNA splicing (SF2/ASF, U5 snRNP) and chromatin remodelling (BRG1, N-CoR deacetylase complexes).

PSKH1

A human kinase that is localized to nuclear speckles but that does not directly interact with SR proteins.

MITOTIC INTERCHROMATIN GRANULES

(MIGS). The speckles (interchromatin granule clusters) that form in the cytoplasm of cells undergoing mitosis, and that increase in number from metaphase to telophase.

REGULATED-EXCHANGE MODEL

A model proposed in this review to account for the basic principles of speckle formation and their dynamic properties.

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Lamond, A., Spector, D. Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4, 605–612 (2003). https://doi.org/10.1038/nrm1172

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