Advertisement

Cell and Tissue Biology

, Volume 4, Issue 2, pp 167–176 | Cite as

Interchromatin granule clusters of mouse preovulatory oocytes: Organization, molecular composition, and possible functions

  • G. N. Pochukalina
  • D. S. Bogolyubov
  • V. N. Parfenov
Article

Abstract

The nuclei of mouse oocytes at the late diplotene stage of meiotic prophase I contain numerous interchromatin granule clusters (IGCs), which are universal, evolutionarily conserved nuclear compartments that are specifically enriched in factors of pre-mRNA splicing. In keeping with the current concepts, IGCs may play an important role in the processes of gene expression by the coupling interconnection of its individual stages, ranging from the transcription to export of mRNA. We have obtained data on the distribution of poly(A)+ RNA, heterogenous nuclear ribonucleoprotein (hnRNP) proteins of the A/B family, and the NXF1/TAP factor of mRNA export in association with IGCs of mouse preovulatory oocytes. In the presented work, using the inhibitor of phosphatases okadaic acid, we have managed to demonstrate the dynamics of large IGCs under the conditions of specific phosphorylation of SR proteins for the first time. The studies were carried out using microinjections of oligonucleotide probes into oocytes, as well as confocal laser scanning and electron microscopy. The problem of the functional significance of IGCs in processes of pre-mRNA metabolism, as well as the participation of IGCs in the organization of mRNA export from the nucleus into the cytoplasm are discussed.

Key words

mouse oocyte nucleus nuclear compartments interchromatin granule clusters metabolism of pre-mRNA poly(A)+ RNA export of mRNA okadaic acid electron microscopy confocal microscopy 

Abbreviations

hnRNP

heterogenous nuclear ribonucleoprotein

IGC

interchromatin granule cluster

mRNA

messenger RNA

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bogolyubov, D., Stepanova, I., and Parfenov, V., Universal Nuclear Domains of Somatic and Germ Cells: Some Lessons from Oocyte Interchromatin Granule Cluster and Cajal Body Structure and Molecular Composition, Bioessays, 2009, vol. 31, pp. 400–409.CrossRefPubMedGoogle Scholar
  2. Bouniol-Baly, C., Hamraoui, L., Guibert, I., Beaujean, N., Szöllösi, M.S., and Debey, P., Differential Transcriptional Activity Associated to Chromatin Configuration in Fully Grown GV Mouse Oocytes, Biol. Reprod., 1999, vol. 60, pp. 580–587.CrossRefPubMedGoogle Scholar
  3. Carter, K.C., Bowman, D., Carrington, W., Fogarty, K., McNeil, J.A., Fay, F.S., and Lawrence, J.B., A Three-Dimensional View of Precursor Messenger RNA Metabolism Within the Mammalian Nucleus, Science, 1993, vol. 259, pp. 1330–1335.CrossRefPubMedGoogle Scholar
  4. Carter, K.C., Taneja, K.L., and Lawrence, J.B., Discrete Nuclear Domains of Poly(A) RNA and Their Relationship to the Functional Organization of the Nucleus, J. Cell Biol., 1991, vol. 115, pp. 1191–1202.CrossRefPubMedGoogle Scholar
  5. Colwill, K., Pawson, T., Andrews, B., Prasad, J., Manley, J.L., Bell, J.C., and Duncan, P.I., The Clk/Sty Protein Kinase Phosphorylates SR Splicing Factors and Regulates Their Intranuclear Distribution, EMBO J., 1996, vol. 15, pp. 265–275.PubMedGoogle Scholar
  6. Daneholt, B., The Transcribed Template and the Transcription Loop in Balbiani Rings, Cell Biol. Int. Rep., 1992, vol. 16, pp. 709–715.CrossRefPubMedGoogle Scholar
  7. Dawson, J.F. and Holmes, C.F.B., Molecular Mechanisms Underlying Inhibition of Protein Phosphatases by Marine Toxins, Frontiers Biosci., 1999, vol. 4, pp. 646–658.CrossRefGoogle Scholar
  8. Dreyfuss, G., Matunis, M.J., Piñol-Roma, S., and Burd, C.G., HnRNP Proteins and the Biogenesis of mRNA, Annu. Rev. Biochem., 1993, vol. 62, pp. 289–321.CrossRefPubMedGoogle Scholar
  9. Dundr, M. and Misteli, T., Functional Architecture in the Cell Nucleus, Biochem. J., 2001, vol. 356, pp. 297–310.CrossRefPubMedGoogle Scholar
  10. Erkmann, J.A. and Kutay, U., Nuclear Export of mRNA: from the Site of Transcription to the Cytoplasm, Exp. Cell Res., 2004, vol. 296, pp. 12–20.CrossRefPubMedGoogle Scholar
  11. Friend, L.R., Han, S.P., Rothnagel, J.A., and Smith, R., Differential Subnuclear Localization of HnRNP a/B Is Dependent on Transcription and Cell Cycle Stage, Biochim. Biophys. Acta, 2008, vol. 1783, pp. 1972–1980.CrossRefPubMedGoogle Scholar
  12. Fu, X.-D. and Maniatis, T., Factor Required for Mammalian Spliceosome Assembly Is Localized to Discrete Regions in the Nucleus, Nature, 1990, vol. 343, pp. 437–441.CrossRefPubMedGoogle Scholar
  13. Gall, J.G., The Centennial of the Cajal Body, Nat. Rev. Mol. Cell Biol., 2003, vol. 4, pp. 975–980.CrossRefPubMedGoogle Scholar
  14. Grüter, P., Tabernero, C., Von Kobbe, C. Schmitt, C., Saavedra, C., Bachi, A., Wilm, M. Felber, B.K., and Izaurralde, E., Tap, the Human Homolog of Mex67P, Mideates Cte-Dependent RNA Export from the Nucleus, Mol. Cell, 1998, vol. 1, pp. 649–659.CrossRefPubMedGoogle Scholar
  15. Hall, L.L., Smith, K.P., Byron, M., and Lawrence, J.B., Molecular Anatomy of a Speckle, Anat. Rec. A Discov. Mol. Cell Evol. Biol., 2006, vol. 288, pp. 664–675.PubMedGoogle Scholar
  16. He, Y. and Smith, R., Nuclear Functions of Heterogeneous Nuclear Ribonucleoproteins A/B, Cell Mol. Biol. Sci., 2009, vol. 66, pp. 1239–1256.Google Scholar
  17. Herold, A., Klymenko, T., and Izaurralde, E., Nxf1/P15 Heterodimers Are Essential for mRNA Nuclear Export in Drosophila, RNA, 2001, vol. 7, pp. 1768–1780.PubMedGoogle Scholar
  18. Herold, A., Teixeira, L., and Izaurralde, E., Genome-Wide Analysis of Nuclear mRNA Export Pathways in Drosophila, EMBO J., 2003, vol. 22, pp. 2472–2483.CrossRefPubMedGoogle Scholar
  19. Hu, Q., Kwon, Y.-S., Nunez, E., Cardamone, M.D., Hutt, K.R., Ohgi, K.A., Carcia-Bassets, I., Rose, D.W., Glass, C.K., Rosenfeld, M.G., and Fu, X.-D., Enhancing Nuclear Receptor-Induced Transcription Requires Nuclear Motor and Lsd1-Dependent Gene Networking in Interchromatin Granules, Proc. Natl. Acad. Sci. USA, 2008, vol. 105, pp. 19199–19204.CrossRefPubMedGoogle Scholar
  20. Huang, S., Deerinck, T.J., Ellisman, M.H., and Spector, D.L., In Vivo Analysis of the Stability and Transport of Nuclear Poly(A) RNA, J. Cell Biol., 1994, vol. 126, pp. 877–899.CrossRefPubMedGoogle Scholar
  21. Ishihama, Y., Tadakuma, H., Tani, T., and Funatsu, T., The Dynamics of pre-mRNAs and Poly(A) RNA at Speckles in Living Cells Revealed by iRFAP Studies, Exp. Cell Res., 2008, vol. 314, pp. 748–762.CrossRefPubMedGoogle Scholar
  22. Izaurralde, E., Nuclear Export of Messenger RNA, Results Probe Cell Differ., 2002, vol. 35, pp. 133–150.Google Scholar
  23. Kaplan, G., Abren, S.I., and Bachvarova, R., R-RNA Accumulation and Protein Synthetic Patterns in Growing Mouse Oocytes, J. Exp. Zool., 1982, vol. 220, pp. 361–370.CrossRefPubMedGoogle Scholar
  24. Lamond, A.I. and Spector, D.L., Nuclear Speckles: A Model for Nuclear Organelles, Nat. Rev. Mol. Cell Biol., 2003, vol. 4, pp. 605–612.CrossRefPubMedGoogle Scholar
  25. Lyon, C.E., Bohmann, K., Sleeman, J., and Lamond, A.I., Inhibition of Protein Dephosphorylation Results in the Accumulation of Splicing snRNPs and Coiled Bodies Within the Nucleolus, Exp. Cell Res., 1997, vol. 230, pp. 84–93.CrossRefPubMedGoogle Scholar
  26. Majlessi, M., Nelson, N.C., and Becker, M.M., Advantages of 2′-O-Methyl Oligoribonucleotide Probes for Detecting RNA Targets, Nucleic Acids Res., 1998, vol. 26, pp. 2224–2229.CrossRefPubMedGoogle Scholar
  27. Matlin, A.J., Clark, F., and Smith, C.W., Understanding Alternative Splicing: Towards a Cellular Code, Nat. Rev. Mol. Cell Biol., 2005, vol. 6, pp. 386–398.CrossRefPubMedGoogle Scholar
  28. Melčák, I., Melčáková, S., Kopský, V., Večeŕová, J., and Raška, I., Prespliceosomal Assembly on Microinjected Precursor mRNA Takes Place in Nuclear Speckles, Mol. Biol. Cell, 2001, vol. 12, pp. 393–406.PubMedGoogle Scholar
  29. Mili, S., Shu, H.J., Zhao, Y., and Piñol-Roma, S., Distinct RNP Complexes of Shuttling hnRNP Proteins with Pre-mRNA and mRNA: Candidate Intermediates in Formation and Export of mRNA, Mol. Cell Biol., 2001, vol. 21, pp. 7307–7319.CrossRefPubMedGoogle Scholar
  30. Misteli, T. and Spector, D.L., The Cellular Organization of Gene Expression, Curr. Opin. Cell Biol., 1998, vol. 10, pp. 323–331.CrossRefPubMedGoogle Scholar
  31. Misteli, T., Beyond the Sequence: Cellular Organization of Genome Function, Cell, 2007, vol. 128, pp. 787–800.CrossRefPubMedGoogle Scholar
  32. Misteli, T., Cáceres, J.F., and Spector, D.L., The Dynamics of a Pre-mRNA Splicing Factor in Living Cells, Nature, 1997, vol. 387, pp. 523–527.CrossRefPubMedGoogle Scholar
  33. Misteli, T., Cell Biology of Transcription and Pre-mRNA Splicing: Nuclear Architecture Meets Nuclear Function, J. Cell Sci., 2000, vol. 113, pp. 1841–1849.PubMedGoogle Scholar
  34. Molenaar, C., Abdulle, A., Gena, A., Tanke, H.J., and Dirks, R.W., Poly(A)+ RNAs Roam the Cell Nucleus and Pass through Speckle Domains in Transcriptionally Active and Inactive Cells, J. Cell Biol., 2004, vol. 165, pp. 191–202.CrossRefPubMedGoogle Scholar
  35. Molenaar, C., Marras, S.A., Slats, J.C., Truffert, J.-C., Lemaitre, M., Raap, A.K., Dirks, R.W., and Tanke, H.J., Linear 2′ O-Methyl RNA Probes for the Visualization of RNA in Living Cells, Nucleic Acids Res., 2001, vol. 29, pp. E89.CrossRefPubMedGoogle Scholar
  36. Monneron, A. and Bernhard, W., Fine Structural Organization of the Interphase Nucleus in Some Mammalian Cells, J. Ultrastruct. Res., 1969, vol. 27, pp. 266–288.CrossRefPubMedGoogle Scholar
  37. Moore, G.P.M., Linten-Moore, S., Peters, H., and Faber, M., RNA Synthesis in the Mouse Oocyte, J. Cell Biol., 1974, vol. 60, pp. 416–422.CrossRefPubMedGoogle Scholar
  38. Nakielny, S. and Dreyfuss, G., Transport of Protein and RNAs in and out of the Nucleus, Cell, 1999, vol. 99, pp. 677–690.CrossRefPubMedGoogle Scholar
  39. Parfenov, V.N., Davis, D., Pochukalina, G., Kostyuchek, D., and Murti, K., Dynamics of Distribution of Splicing Components Relative to the Transcriptional State of Human Oocytes from Antral Follicles, J. Cell Biochem., 1998, vol. 69, pp. 72–80.CrossRefPubMedGoogle Scholar
  40. Parfenov, V.N., Davis, D.S., Pochukalina, G.N., Kostyuchek, D., and Murti, K.G., Nuclear Distribution of RNA Polymerase II in Human Oocytes from Antral Follicles: Dynamics Relative to the Transcriptional State and Association with Splicing Factors, J. Cell. Biochem., 2000, vol. 77, pp. 654–665.CrossRefPubMedGoogle Scholar
  41. Parfenov, V.N., Pochukalina, G.N., Davis, D.S., Reinbold, R., Schöler, H.R., and Murti, K.G., Nuclear Distribution of Oct-4 Transcription Factor in Transcriptionally Active and Inactive Mouse Oocytes and Its Relation to RNA Polymerase II and Splicing Factors, J. Cell Biochem., 2003, vol. 89, pp. 720–732.CrossRefPubMedGoogle Scholar
  42. Parfenov, V.N., Pochukalina, G., Dudina, L., Kostyuchek, D., and Gruzova, M., Human Antral Follicles: Oocyte Nucleus and the Karyosphere Formation (Electron Microscopic and Autoradigraphic Data), Gamete Res., 1989, vol. 22, pp. 219–231.CrossRefPubMedGoogle Scholar
  43. Piñol-Roma, S. and Dreyfuss, G., Shuttling of pre-mRNA Binding Proteins between Nucleus and Cytoplasm, Nature, 1992, vol. 355, pp. 730–732.CrossRefPubMedGoogle Scholar
  44. Piñol-Roma, S. and Dreyfuss, G., HnRNP Proteins: Localization and Transport between the Nucleus and the Cytoplasma, Trends Cell Biol., 1993, vol. 3, pp. 151–155.CrossRefPubMedGoogle Scholar
  45. Pochukalina, G.N. and Parfenov, V.N., Nucleolus Transformation in Oocytes of Mouse Antral Follicles. Revealing of Coilin and RNA Polymerase I Complex Components, Tsitologiia, 2008, vol. 50, no. 8, pp. 671–680.PubMedGoogle Scholar
  46. Pochukalina, G.N. and Parfenov, V.N., The Nucleolus in Oocytes of Multylayer Mouse Follicles: Topography of Fibrillarin, RNA Polymerase I and Coilin, Tsitologiia, 2006, vol. 48, no. 8, pp. 641–652.PubMedGoogle Scholar
  47. Pochukalina, G.N., Davis, D.S., Kostiuchek, D.F., Murti, K.G., and Parfenov, V.N. Splicing Factors in Oocyte Nuclei from Human Antral Follicles, Tsitologiia, 1998, vol. 40, no. 4, pp. 237–249.Google Scholar
  48. Prasanth, K.V. and Spectro, D.L., Eukaryotic Regulatory RNAs: An Answer to the “Genome Complexity” Conundrum, Genes Dev., 2007, vol. 21, pp. 11–42.CrossRefPubMedGoogle Scholar
  49. Reed, R. and Hurt, E., A Conserved mRNA Export Machinery Coupled to pre-mRNA Splicing, Cell, 2002, vol. 108, pp. 523–531.CrossRefPubMedGoogle Scholar
  50. Sacco-Bubulya, P. and Spector, D.L., Disassembly of Interchromatin Granule Clusters Alters the Coordination of Transcription and pre-mRNA Splicing, J. Cell Biol., 2002, vol. 156, pp. 425–436.CrossRefPubMedGoogle Scholar
  51. Saitoh, N., Spahr, C.S., Patterson, S.D., Bubulya, P., Neuwald, A.F., and Spector, D.L., Proteomic Analysis of Interchromatin Granule Clusters, Mol. Biol. Cell, 2004, vol. 15, pp. 3876–3890.CrossRefPubMedGoogle Scholar
  52. Schmidt, U., Richter, K., Berger, A.B., and Lichter, P., In Vivo BiFC Analysis of Y14 and Nxf1 mRNA Export Complexes: Preferential Localization within and around SC35 Domains, J. Cell Biol., 2006, vol. 172, pp. 373–381.CrossRefPubMedGoogle Scholar
  53. Shopland, L.S., Johnson, C.V. Byron, M., McNeil, J., and Lawrence, J.B., Clustering of Multiple Specific Genes and Gene-Rich R-Bands around SC-35 Domains: Evidence for Local Euchromatic Neighborhoods, J. Cell Biol., 2003, vol. 162, pp. 981–990.CrossRefPubMedGoogle Scholar
  54. Shopland, L.S., Johnson, C.V., and Lawvence, J.B., Evidence That All Sc-35 Domains Contain mRNAs and That Transcripts Can Be Structurally Constrained within These Domains, J. Struct. Biol., 2002, vol. 140, pp. 131–139.CrossRefPubMedGoogle Scholar
  55. Spector, D.L., Macromolecular Domains within the Cell Nucleus, Annu. Rev. Cell Biol. USA, 1993, vol. 9, pp. 265–315.CrossRefGoogle Scholar
  56. Stepanova, I.S., Bogolyubov, D.S., Skovorodkin I.N., and Parfenov, V.N., Cajal Bodies and Interchromatin Granule Clusters in Cricket Oocytes: Composition, Dynamics and Interactions, Cell Biol. Int., 2007, vol. 31, pp. 203–214.CrossRefPubMedGoogle Scholar
  57. Tan, W., Zoltukhin, A.S., Bear, J., Patenaude, D.J., and Felber, B.K., The mRNA Export in Caenorhabditis elegans Is Mediated by Ce-Nxf-1, an Ortholog of Human Tap/Nxf and Saccharomyces cerevisiae Mex67P, RNA, 2000, vol. 6, pp. 1762–1772.CrossRefPubMedGoogle Scholar
  58. Tanuma, N., Kim, S.-E., Beullens, M., Tsubali, Y., Mitsuhashi, S., Nomura, M., Kawamura, T., Isono, K., Koseki, H., Sato, M., Bollen, M., Kikuchi, K., and Shima, H., Nuclear Inhibitor of Protein Phosphatase-1 (NIPP1) Direct Protein Phosphatase-1 (PP1) to Dephosphorylate the U2 snRNP Component, Spliceosome-Associated Protein 155 (Sap155), J. Biol. Chem., 2008, vol. 283, pp. 35 805–35 814.CrossRefGoogle Scholar
  59. Visa, N., Alzhanova-Ericsson, A.T., Sun, X., Kiseleva, E., Bjorkroth, B., Wurtz, T., and Daneholt, B., A Pre-mRNA-Binding Protein Accompanies the RNA from the Gene Through the Nuclear Pores and into Polysomes, Cell, 1996, vol. 84, 253–264.CrossRefPubMedGoogle Scholar
  60. Visa, N., Puvion-Dutilleul, F., Harper, F., Bachellerie, J.P., and Puvion, E., Intranuclear Distribution of Poly(A)+ RNA Determined by Electron Microscope in situ Hybridization, Exp. Cell Res., 1993, vol. 208, pp. 19–34.CrossRefPubMedGoogle Scholar
  61. Wang, H.C., Sassano, D., Blume, A.J., and Ziai, M.R., Gene Expression in Xenopus Oocytes, Int. J. Biochem., 1991, vol. 23, pp. 271–276.CrossRefPubMedGoogle Scholar
  62. Will, C.L. and Lührmann, R., Protein Functions in pre-mRNA Splicing, Curr. Opin. Cell Biol., 1997, vol. 9, pp. 320–328.CrossRefPubMedGoogle Scholar
  63. Wu, J.Y. and Maniatis, T., Specific Interactions Between Proteins Implicated in Splice Site Selection and Regulated Alternative Splicing, Cell, 1993, vol. 75, pp. 1061–1070.CrossRefPubMedGoogle Scholar
  64. Zatsepina, O.V., Bouniol-Baly, C., Amiroand, C., and Debey, P., Functional and Molecular Reorganization of the Nucleolar Apparatus in Maturing Mouse Oocytes, Dev. Biol., 2000, vol. 223, pp. 354–370.CrossRefPubMedGoogle Scholar
  65. Zhou, Z., Luo, M.J., Straesser, K., Katahira, J., Hurt, E., and Reed, R., The Protein Aly Links Pre-Messenger-RNA Splicing to Nuclear Export in Metazoans, Nature, 2000, vol. 407, pp. 401–405.CrossRefPubMedGoogle Scholar
  66. Zybina, E.V., Synthesis of RNA and Protein in the Developing Ovum and Follicle of Mice, Tsitologiia, 1971, vol. 13, pp. 768–775.PubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • G. N. Pochukalina
    • 1
  • D. S. Bogolyubov
    • 1
  • V. N. Parfenov
    • 1
  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

Personalised recommendations