Glycoconjugate Journal

, Volume 19, Issue 7–9, pp 499–506

Understanding the biochemical activities of galectin-1 and galectin-3 in the nucleus

  • Ronald J. Patterson
  • Weizhong Wang
  • John L. Wang


Nuclear extracts (NE), capable of carrying out splicing of pre-mRNA, contain galectin-1 and galectin-3. NE depleted of galectins-1 and -3 concomitantly lose their splicing activity. The activity of the galectin-depleted extract can be reconstituted by the addition of either galectin-1 or galectin-3. These results suggest that galectins-1 and -3 serve as redundant splicing factors. Consistent with this notion, immunofluorescence staining showed that both galectins yielded a diffuse nucleoplasmic distribution, matching that of nascent transcripts and consistent with the hypothesis that bulk transcription and pre-mRNA processing occur throughout the nucleoplasm. Under some conditions, the galectins could be found in speckled structures and nuclear bodies but the prevailing thought is that these represent sites of storage and recycling rather than sites of action. Galectin-1 and galectin-3 bind directly to Gemin4, a component of the SMN core complex, which plays multiple roles in ribonucleoprotein assembly, including the biogenesis, delivery, and recycling of snRNPs to the spliceosome. Thus, galectin-1 and galectin-3 constitute a part of an interacting dynamic network of many factors involved in the splicing and transport of mRNA. Published in 2004.

lectins pre-mRNA splicing spliceosomes ribonucleoprotein complexes gems and nuclear bodies 


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  1. 1.
    Barondes SH, Castronovo V, Cooper DNW, Cummings RD, et al., Galectins: A family of animal β-galactoside-binding lectins, Cell 76, 597-8 (1994).Google Scholar
  2. 2.
    Hughes RC, Secretion of the galectin family of carbohydratebinding proteins, Biochim Biophys Acta, 1473, 172-85 (1999).Google Scholar
  3. 3.
    Leffler H, Galectins structure and function—A synopsis, Results Probl Cell Diff, 33, 57-83 (2001).Google Scholar
  4. 4.
    Wilson TJG, Firth MN, Powell JT, Harrison FL, The sequence of the mouse 14 kDa β-galactoside-binding lectin and evidence for its synthesis on free cytoplasmic ribosomes, Biochem J, 261, 847-52 (1989).Google Scholar
  5. 5.
    Clerch LB, Whitney P, Hass M, Brew K, Miller T, Werner R, Massaro D, Sequence of a full-length cDNA for rat lung β?-galactoside-binding protein: Primary and secondary structure of the lectin, Biochemistry, 27, 692-9 (1988).Google Scholar
  6. 6.
    Herrmann J, Turck CW, Atchison RE, Hufleijt ME, Poulter L, Gitt MA, Burlingame AL, Barondes SH, Leffler H, Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase, J Biol Chem, 268, 26704-11 (1993).Google Scholar
  7. 7.
    Vyakarnam A, Lenneman AJ, Lakkides KM, Patterson RJ, Wang JL, A comparative nuclear localization study of galectin-1 with other splicing components, Exp Cell Res, 242, 419-28 (1998).Google Scholar
  8. 8.
    Akimoto Y, Kawakami H, Oda Y, Obinata A, Endo H, Kasai K, Hirano H, Changes in expression of the endogenous β-galactosidebinding 14_ kDa lectin of chick embryonic skin during epidermal differentiation, Exp Cell Res, 199, 297-304 (1992).Google Scholar
  9. 9.
    Choi JY, van Wijnen AJ, Aslam F, Leszyk JD, Stein JL, Stein GS, Lian JB, Penman S, Developmental association of the β-galactoside-binding protein galectin-1 with the nuclear matrix of rat calvarial osteoblasts, J Cell Sci, 111, 3035-43 (1998).Google Scholar
  10. 10.
    Moutsatsos IK, Davis JM, Wang JL, Endogenous lectins from cultured cells: Subcellular localization of carbohydrate-binding protein 35 in 3T3 fibroblasts, J Cell Biol, 102, 477-83 (1986).Google Scholar
  11. 11.
    Hubert M, Wang S-Y, Wang JL, Seve A-P, Hubert J, Intranuclear distribution of galectin-3 in mouse 3T3 fibroblasts: Comparative analyses by immunofluorescence and immunoelectron microscopy, Exp Cell Res, 220, 397-406 (1995).Google Scholar
  12. 12.
    Craig SS, Krishnaswamy P, Irani A-M, Kepley CL, Liu F-T, Schwartz LB, Immunoelectron microscopic localization of galectin-3, an IgE binding protein, in human mast cells and basophils, Anat Rec, 242, 211-9 (1995).Google Scholar
  13. 13.
    Lotz MM, Andrews, CW, Korzelius CA, Lee EC, Steele GD, Clarke A, Mercurio AM, Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with neoplastic progression of colon carcinoma, Proc Natl Acad Sci USA, 90, 3466-70 (1993).Google Scholar
  14. 14.
    van den Brule FA, Waltregny D, Liu F-T, Castronovo V, Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates with prostate carcinoma progression, Int J Cancer, 89, 361-7 (2000).Google Scholar
  15. 15.
    Magnaldo T, Fowlis D, Darmon M, Galectin-7, a marker of all types of stratified epithelia, Differentiation, 63, 159-68 (1998).Google Scholar
  16. 16.
    Kuwabara I, Kuwabara Y, Yang R-Y, Schuler M, Green DR, Hsu DK, Liu F-T, Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release, J Biol Chem, 277, 3487-97 (2002).Google Scholar
  17. 17.
    Dvorak AM, Furitsu T, Letourneau L, Ishizaka T, Ackerman SJ, Mature eosinophils stimulated to develop in human cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. Part I. Piecemeal degranulation of specific granules and distribution of Charcot-Leyden crystal protein, Am J Pathol 138 69-82 (1991).Google Scholar
  18. 18.
    Dunphy JL, Balic A, Barcham GJ, Horvath AJ, Nash AD, Meeusen ENT, Isolation and characterization of a novel inducible mammalian galectin, J Biol Chem, 275, 32106-13 (2000).Google Scholar
  19. 19.
    Yang R-Y, Hsu DK, Yu L, Ni J, Liu F-T, Cell cycle regulation by galectin-12, a new member of the galectin superfamily, J Biol Chem, 276, 2025 2-60 (2001).Google Scholar
  20. 20.
    Hotta K, Funahashi T, Matsukawa Y, Takahashi M, et al., Galectin-12, an adipocyte-expressed galectin-like molecule possessing apoptosis-inducing activity, J Biol Chem, 276, 34089-97 (2001).Google Scholar
  21. 21.
    Yang Q-S, Ying K., Yuan H-L, Chen J-Z, Meng X-F, Wang Z, Xie Y, Mao Y-M, Cloning and expression of a novel human galectin cDNA, predominantly expressed in placenta, Biochim Biophys Acta, 1574, 407-11 (2001).Google Scholar
  22. 22.
    Dunphy JL, Barcham GJ, Bischof RJ, Young AR, Nash A, Meeusen ENT, Isolation and characterization of a novel eosinophil-specific galectin released into the lungs in response to allergen challenge, J Biol Chem, 277, 14916-24 (2002).Google Scholar
  23. 23.
    Moutsatsos IK, Wade M, Schindler M, Wang JL, Endogenous lectins from cultured cells: Nuclear localization of carbohydratebinding protein 35 in proliferating 3T3 fibroblasts, Proc Natl Acad Sci USA, 84, 6452-56 (1987).Google Scholar
  24. 24.
    Xing Y, Lawrence JB, Preservation of specific RNA distribution within the chromatin-depleted nuclear substructure demonstrated by in situ, hybridization coupled with biochemical fractionation, J Cell Biol, 112, 1055-63 (1991).Google Scholar
  25. 25.
    Fey EG, Krochmalnic G, Penman, S, The non-chromatin substructures of the nucleus: The ribonucleoprotein (RNP)-containing and RNP-depeleted matrices analyzed by sequential fractionation and resinless section electron microscopy, J Cell Biol, 102, 1654-65 (1986)Google Scholar
  26. 26.
    Laing JG, Wang JL, Identification of carbohydrate binding protein 35 in heterogeneous nuclear ribonucleoprotein (hnRNP) complex, Biochemistry, 27, 5329-34 (1988).Google Scholar
  27. 27.
    Vyakaranam A, Dagher SF, Wang JL, Patterson RJ, Evidence for a role for galectin-1 in pre-mRNA splicing, Mol Cell Biol, 17, 4730-37 (1997).Google Scholar
  28. 28.
    Spector DL, Fu XD, Maniatis T, Associations between distinct pre-mRNA splicing components and the cell nucleus, EMBO J 10, 3467-81 (1991).Google Scholar
  29. 29.
    Andrade LEC, Chan EKI, Raska I, Peebles CL, Roos G, Tan EM, Human autoantibody to a novel protein of the nuclear coiled body: Immunological characterization and cDNA cloning of p80 coilin, J Exp Med, 173, 1407-19 (1991).Google Scholar
  30. 30.
    Liu Q, Dreyfuss G, A novel nuclear structure containing the survival of motor neurons protein, EMBO J, 15, 3555-65 (1996).Google Scholar
  31. 31.
    Fakan S, Puvion E, The ultrastructural visualization of nucleolar and extranucleolar RNA synthesis and distribution, Int Rev Cytol 65, 255-99 (1980).Google Scholar
  32. 32.
    Spector DL, O'Keefe, RT, Jimenez-Garcia LF, Dynamics of transcription and pre-mRNA splicing within the mammalian cell nucleus, Cold Spring Harbor Symp Quant Biol, 58, 799-805 (1993).Google Scholar
  33. 33.
    Fakan S, Puvion E, Sphor G, Localization and characterization of newly synthesized nuclear RNA in isolated rat hepatocytes, Exp Cell Res, 99, 155-64 (1976).Google Scholar
  34. 34.
    Zhang G, Taneja KL, Singer RH, Green, MR, Localization of pre-mRNA splicing in mammalian nuclei, Nature, 372, 809-12 (1994).Google Scholar
  35. 35.
    Fakan S, Leser G, Martin TE, Ultrastructural distribution of nuclear ribnonucleoproteins as visualized by immunocytochemistry on thin sections, J Cell Biol, 98, 358-63 (1984).Google Scholar
  36. 36.
    Puvion E, Viron A, Assens C, Leduc EH, Jeanteur P, Immunocytochemical identification of nuclear structures containing snRNPs in isolated rat liver cells, J Ultrastruct Res, 87, 180-9 (1984).Google Scholar
  37. 37.
    Lewis JD, Tollervey D, Like attracts like: Getting RNA processing together in the nucleus, Science, 288, 1385-9 (2000).Google Scholar
  38. 38.
    Zeng C, Kim E, Warren, SL, Berget SM, Dynamic relocation of transcription and splicing factors dependent upon transcriptional activity, EMBO J, 16, 1401-12 (1997).Google Scholar
  39. 39.
    Gama-Carvalho M, Krauss RD, Chiang L, Valcarcel J, Green MR, Carmo-Fonseca M, Targeting U2AF65 to sites of active splicing in the nucleus, J Cell Biol, 137, 975-87 (1997).Google Scholar
  40. 40.
    Lamond AI, Earnshaw WC, Structure and function in the nucleus, Science, 280, 547-53 (1998).Google Scholar
  41. 41.
    Spector DL, Macromolecular domains within the cell nucleus, Annu Rev Cell Dev Biol, 9, 265-315 (1993).Google Scholar
  42. 42.
    Zillman M, Zapp ML, Berget SM, Gel electrophoretic isolation of splicing complexes containing U1 small nuclear ribonucleoprotein particles, Mol Cell Biol, 8, 814-21 (1988).Google Scholar
  43. 43.
    Konarska MM, Sharp PA, Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs, Cell, 46, 845-55 (1986).Google Scholar
  44. 44.
    Michaud S, Reed R, A functional association between the 5' and 3' splice site is established in the earliest prespliceosome complex (E) in mammals, Genes Dev, 7, 1008-20 (1993).Google Scholar
  45. 45.
    Dagher SF, Wang JL, Patterson RJ, Identification of galectin-3 as a factor in pre-mRNA splicing, Proc Natl Acad Sci USA, 92, 1213-7 (1995).Google Scholar
  46. 46.
    Park, JW, Voss PG, Grabski S, Wang JL, Patterson RJ, Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the SMN protein, Nucleic Acids Res, 27, 3595-602 (2001).Google Scholar
  47. 47.
    Patterson RJ, Dagher SF, Vyakarnam A, Wang JL, Nuclear galectins: Functionally redundant components in processing of pre-mRNA, Trends Glycosci Glycotechnol, 9, 77-85 (1997).Google Scholar
  48. 48.
    Colnot C, Fowlis D, Ripoche MA, Bouchaert I, Poirier F, Embryonic implantation in galectin-1/galectin-3 double mutant mice, Dev Dyn, 211, 306-13 (1998).Google Scholar
  49. 49.
    Hirabayashi J, Arata Y, Kasai K, Galectins from the nematode Caenorhabditis elegans, and the genome project, Trends Glycosci Glycotechnol, 9, 113-22 (1997).Google Scholar
  50. 50.
    Nomura K, Mizuguchi S, Mitani S, Gengyo-Ando K, Hirabayashi Y, Nomura KH, Systematic analysis of genes involved in glycome formation of the nematode Caenorhabditis elegans, XVI International Symposium on Glycoconjugates, Abstract C4.5, 34 (2001).Google Scholar
  51. 51.
    Charroux B, Pellizzoni L, Perkinson RA, Yong J, Shevchenko A, Mann M, Dreyfuss G, Gemin 4: A novel component of the SMN complex that is found in both gems and nucleoli, J Cell Biol, 148, 1177-86 (2000).Google Scholar
  52. 52.
    Paushkin S, Gubitz AK, Massenet S, Dreyfuss G, The SMN complex, an assemblysome of ribonucleoproteins, Curr Opin Cell Biol 14, 305-12 (2002).Google Scholar
  53. 53.
    Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G, Identification and characterization of Gemin7, a novel component of the SMN complex, J Biol Chem, 277, 31957-62 (2002).Google Scholar
  54. 54.
    Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G, A functional interaction between the survival motor neuron complex and RNA polymerase II, J Cell Biol, 152, 75-85 (2001).Google Scholar
  55. 55.
    Fischer U, Liu Q, Dreyfuss G, The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis, Cell, 90, 1023-9 (1997).Google Scholar
  56. 56.
    Meister G, Buhler D, Pillai R, Lottspeich F, Fischer U, Amultiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs, Nature Cell Biol, 3, 945-9 (2001).Google Scholar
  57. 57.
    Pellizzoni L, Kataoka N, Charroux B, Dreyfuss G, A novel function for SMN, the spinal muscular atrophy disease gene product, in premRNA splicing, Cell, 95, 615-24 (1998).Google Scholar
  58. 58.
    Gong HC, Honjo Y, Nangia-Makker P, Hogan V, Mazurak N, Bresalier RS, Raz A, The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells, Cancer Res, 59, 6239-45 (1999).Google Scholar
  59. 59.
    Gaudin JC, Mehul B, Hughes RC, Nuclear localisation of wild type and mutant galectin-3 in transfected cells, Biol Cell, 92, 49-58 (2000).Google Scholar
  60. 60.
    Nakielny S, Dreyfuss G, Transport of proteins and RNAs in and out of the nucleus, Cell, 99, 677-90 (1999).Google Scholar
  61. 61.
    Davidson PJ, Davis MJ, Patterson RJ, Ripoche MA, Poirier F, Wang, JL, Shuttling of galectin-3 between the nucleus and cytoplasm, Glycobiology, 12, 329-37 (2002).Google Scholar
  62. 62.
    Tsay YG, Lin NY, Voss PG, Patterson RJ, Wang JL, Export of galectin-3 from nuclei of digitonin-permeabilized mouse 3T3 fibroblasts, Exp Cell Res, 252, 250-62 (1999).Google Scholar
  63. 63.
    Liu FT, Patterson RJ, Wang JL, Intracellular functions of galectins, Biochim Biophys Acta, 1572, 263-73 (2002).Google Scholar
  64. 64.
    Iwahasi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y, Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy, Nature, 390, 413-7 (1997).Google Scholar
  65. 65.
    Lefebvre S, Burglen L, Frezal J, Munnich A, Melki J, The role of the SMN gene in proximal spinal muscular atrophy, Hum Mol Genet, 7, 1531-6 (1998).Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Ronald J. Patterson
    • 1
  • Weizhong Wang
    • 1
  • John L. Wang
    • 2
  1. 1.Department of Microbiology and Molecular GeneticsMichigan State UniversityEast LansingUSA
  2. 2.Department of Biochemistry and Molecular BiologyMichigan State UniversityEast LansingUSA

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