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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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UAP56- a key player with surprisingly diverse roles in pre-mRNA splicing and nuclear export

  • Shen, Hai-Hong (Department of Life Science, Gwangju Institute of Science and Technology)
  • Published : 2009.04.30
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Abstract

Transcripts contain introns that are usually removed from premessenger RNA (MRNA) in the process of pre-mRNA splicing. After splicing, the mature RNA is exported from the nucleus to the cytoplasm. The splicing and export processes are coupled. UAP56 protein, which is ubiquitously present in organisms from yeasts to humans, is a DExD/H-box family RNA helicase that is an essential splicing factor with various functions in the prespliceosome assembly and mature spliceosome assembly. Collective evidence indicates that UAP56 has an essential role in mRNA nuclear export. This mini-review summarizes recent evidence for the role of UAP56 in pre-mRNA splicing and nuclear export.

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References

  1. Fleckner, J., Zhang, M., Valcarcel, J. and Green, M. R. (1997) U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 11, 1864-1872 https://doi.org/10.1101/gad.11.14.1864
  2. Shen, H., Zheng, X., Shen, J., Zhang, L., Zhao, R. and Green, M. R. (2008) Distinct activities of the DExD/H-boxsplicing factor hUAP56 facilitate stepwise assembly of the spliceosome. Genes Dev. 22, 1796-1803 https://doi.org/10.1101/gad.1657308
  3. Shen, J., Zhang, L. and Zhao, R. (2007) Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J. Biol. Chem. 282, 22544-22550 https://doi.org/10.1074/jbc.M702304200
  4. Kistler, A. L. and Guthrie, C. (2001) Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for sub2, an essential spliceosomal ATPase. Genes Dev. 15, 42-49 https://doi.org/10.1101/gad.851301
  5. Gatfield, D., Le Hir, H., Schmitt, C., Braun, I. C., Kocher, T., Wilm, M. and Izaurralde, E. (2001) The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Curr. Biol. 11, 1716-1721 https://doi.org/10.1016/S0960-9822(01)00532-2
  6. Luo, M-J. and Reed, R. (1999) Splicing is required for rapid and efficient mRNA export in metazoans. Proc. Natl. Acad. Sci. U.S.A. 96, 14937-14942 https://doi.org/10.1073/pnas.96.26.14937
  7. Luo, M. L., Zhou, Z., Magni, K., Christoforides, C., Rappsilber, J., Mann, M. and Reed, R. (2001) Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 413, 644-647 https://doi.org/10.1038/35098106
  8. Meignin, C. and Davis, I. (2008) UAP56 RNA helicase is required for axis specification and cytoplasmic mRNA localization in Drosophila. Dev. Biol. 315, 89-98 https://doi.org/10.1016/j.ydbio.2007.12.004
  9. Zhao, R., Shen, J., Green, M. R., MacMorris, M. and Blumenthal, T. (2004) Crystal structure of UAP56, a DExD/H-box protein involved in pre-mRNA splicing and mRNA export. Structure 12, 1373-1381 https://doi.org/10.1016/j.str.2004.06.006
  10. Benz, J., Trachsel, H. and Baumann, U. (1999) Crystal structure of the ATPase domain of translation initiation factor 4A from Saccharo- myces cerevisiae - the prototype of the DEAD box protein family. Struct. Fold. Des. 7, 671-679 https://doi.org/10.1016/S0969-2126(99)80088-4
  11. Caruthers, J. M. and McKay, D. B. (2002) Helicase structure and mechanism. Curr. Opin. Struct. Biol. 12, 23-133
  12. Kota, K. P., Wagner, S. R., Huerta, E., Underwood, J. M. and Nickerson, J. A. (2008) Binding of ATP to UAP56 is necessary for mRNA export. J. Cell Sci. 121, 1526-1537 https://doi.org/10.1242/jcs.021055
  13. Eperon, I. C., Makarova, O. V., Mayeda, A., Munroe, S. H., Caceres, J. F., Hayward, D. G. and Krainer, A. R. (2000) Selection of alternative 5' splice sites: role of U1 snRNP and models for the antagonistic effects of SF2/ASF and hnRNP A1. Mol. Cell Biol. 20, 8303-8318 https://doi.org/10.1128/MCB.20.22.8303-8318.2000
  14. Hertel, K. J. and Graveley, B. R. (2005) RS domains contact the pre-mRNA throughout spliceosome assembly. Trends Biochem. Sci. 30, 115-118 https://doi.org/10.1016/j.tibs.2005.01.002
  15. Kan, J. L. and Green, M. R. (1999) Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor. Genes Dev. 13, 462-471 https://doi.org/10.1101/gad.13.4.462
  16. Shen, H., Kan, J. L. and Green, M. R. (2004) Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly. Mol. Cell 13, 367-376 https://doi.org/10.1016/S1097-2765(04)00025-5
  17. Shen, H. and Green, M. R. (2007) RS domain-splicing signal interactions in splicing of U12-type and U2-type introns. Nat. Struct. Mol. Biol. 14, 597-603 https://doi.org/10.1038/nsmb1263
  18. Shen, H. and Green, M. R. (2006) RS domains contact splicing signals and promote splicing by a common mechanism in yeast through humans. Genes Dev. 20, 1755-1765 https://doi.org/10.1101/gad.1422106
  19. Shen, H., Kan, J. L., Ghigna, C., Biamonti, G. and Green, M. R. (2004) A single polypyrimidine tract binding protein (PTB) binding site mediates splicing inhibition at mouse IgM exons M1 and M2. RNA 10, 787-794 https://doi.org/10.1261/rna.5229704
  20. Cartegni, L. and Krainer, A. R. (2002) Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat. Genet. 30, 377-384 https://doi.org/10.1038/ng854
  21. Shin, C. and Manley, J. L. (2004) Cell signalling and the control of pre-mRNA splicing. Nat. Rev. Mol. Cell Biol. 5, 727-738 https://doi.org/10.1038/nrm1467
  22. Cordin, O., Banroques, J., Tanner, N. K. and Linder, P. (2006) The DEAD-box protein family of RNA helicases. Gene 367, 17-37 https://doi.org/10.1016/j.gene.2005.10.019
  23. Fairman, M. E., Maroney, P. A., Wang, W., Bowers, H. A., Gollnick, P., Nilsen, T. W. and Jankowsky, E. (2004) Protein displacement by DExH/D 'RNA helicases' without duplex unwinding. Science 304, 730-734 https://doi.org/10.1126/science.1095596
  24. Laggerbauer, B., Achsel, T. and Luhrmann, R. (1998) The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc. Natl. Acad. Sci. U.S.A. 95, 4188-4192 https://doi.org/10.1073/pnas.95.8.4188
  25. Linder, P. (2006) Dead-box proteins: a family affair--active and passive players in RNP-remodeling. Nucleic. Acids Res. 34, 4168-4180 https://doi.org/10.1093/nar/gkl468
  26. Raghunathan, P. L. and Guthrie, C. (1998) RNA unwindingin U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr. Biol. 8, 847-855 https://doi.org/10.1016/S0960-9822(07)00345-4
  27. Rocak, S. and Linder, P. (2004) DEAD-box proteins: the driving forces behind RNA metabolism. Nat. Rev. Mol. Cell Biol. 5, 232-241 https://doi.org/10.1038/nrm1335
  28. Sengoku, T., Nureki, O., Nakamura, A., Kobayashi, S. and Yokoyama, S. (2006) Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa. Cell 125, 287-300 https://doi.org/10.1016/j.cell.2006.01.054
  29. Silverman, E., Edwalds-Gilbert, G. and Lin, R. J. (2003) DExD/H-box proteins and their partners: helping RNA helicases unwind. Gene 312, 1-16 https://doi.org/10.1016/S0378-1119(03)00626-7
  30. Staley, J. P. and Guthrie, C. (1998) Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell 92, 315-326 https://doi.org/10.1016/S0092-8674(00)80925-3
  31. Wagner, J. D., Jankowsky, E., Company, M., Pyle, A. M. and Abelson, J. N. (1998) The DEAH-box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release from the spliceosome and unwinds RNA duplexes. EMBO J. 17, 2926-2937 https://doi.org/10.1093/emboj/17.10.2926
  32. Wang, Y., Wagner, J. D. and Guthrie, C. (1998) The DEAH-box splicing factor Prp16 unwinds RNA duplexes in vitro. Curr. Biol. 8, 441-451 https://doi.org/10.1016/S0960-9822(98)70178-2
  33. Zhang, M. and Green, M. R. (2001) Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. Genes Dev. 15, 30-35 https://doi.org/10.1101/gad.851701
  34. Blencowe, B. J., Issner, R., Nickerson, J. A. and Sharp, P. A. (1998) A coactivator of pre-mRNA splicing. Genes Dev. 12, 996-1009 https://doi.org/10.1101/gad.12.7.996
  35. Chan, C. C., Dostie, J., Diem, M. D., Feng, W., Mann, M., Rappsilber, J. and Dreyfuss, G. (2004) eIF4A3 is a novel component of the exon junction complex. RNA 10, 200-209 https://doi.org/10.1261/rna.5230104
  36. Cheng, H., Dufu, K., Lee, C. S., Hsu, J. L., Dias, A. and Reed, R. (2006) Human mRNA export machinery recruited to the 5_ end of mRNA. Cell 127, 1389-1400 https://doi.org/10.1016/j.cell.2006.10.044
  37. Maniatis, T. and Tasic, B. (2002) Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418, 236-243 https://doi.org/10.1038/418236a
  38. Mandel, C. R., Bai, Y. and Tong, L. (2008) Protein factors in pre-mRNA 3'-end processing. Cell Mol. Life Sci. 65, 1099-1122 https://doi.org/10.1007/s00018-007-7474-3
  39. Jensen, T. H., Boulay, J., Rosbash, M. and Libri, D. (2001) The DECD box putative ATPase Sub2p is an early mRNA export factor. Curr. Biol. 11, 1711-1715 https://doi.org/10.1016/S0960-9822(01)00529-2
  40. Gatfield, D., Le Hir, H., Schmitt, C., Braun, I. C., Kocher, T., Wilm, M. and Izaurralde, E. (2001) The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Curr. Biol. 11, 1716-1721 https://doi.org/10.1016/S0960-9822(01)00532-2
  41. Linder, P. and Stutz, F. (2001) mRNA export: travelling with DEAD box proteins. Curr. Biol. 11, R961-963 https://doi.org/10.1016/S0960-9822(01)00574-7
  42. Strasser, K., Masuda, S., Mason, P., Pfannstiel, J., Oppizzi, M., Rodriguez-Navarro, S., Rondon, A. G., Aguilera, A., Struhl, K., Reed, R. and Hurt, E. (2002) TREX is a conserved complex coupling transcription with messenger RNA export. Nature 417, 304-308 https://doi.org/10.1038/nature746
  43. Kiesler, E., Miralles, F. and Visa, N. (2002) HEL/UAP56 binds cotranscriptionally to the Balbiani ring pre-mRNA in an intron-independent manner and accompanies the BR mRNP to the nuclear pore. Curr. Biol. 12, 859-862 https://doi.org/10.1016/S0960-9822(02)00840-0
  44. Herold, A., Teixeira, L. and Izaurralde, E. (2003) Genomewide analysis of nuclear mRNA export pathways in Drosophila. EMBO J. 22, 2472-2483 https://doi.org/10.1093/emboj/cdg233
  45. MacMorris, M., Brocker, C. and Blumenthal, T. (2003) UAP56 levels affect viability and mRNA export in Caenorhabditis elegans. RNA 9, 847-857 https://doi.org/10.1261/rna.5480803
  46. Thakurta, A. G., Selvanathan, S. P., Patterson, A. D., Gopal, G. and Dhar, R. (2007) The nuclear export signal of splicing factor Uap56p interacts with nuclear pore-associated protein Rae1p for mRNA export in Schizosaccharomyces pombe. J. Biol. Chem. 282,17507-17516 https://doi.org/10.1074/jbc.M609727200
  47. Taniguchi, I. and Ohno, M. (2008) ATP-dependent recruitment of export factor Aly/REF onto intronless mRNAs by RNA helicase UAP56. Mol. Cell Biol. 28, 601-608 https://doi.org/10.1128/MCB.01341-07
  48. Meignin, C. and Davis, I. (2008) UAP56 RNA helicase is required for axis specification and cytoplasmic mRNA localization in Drosophila. Dev. Biol. 315, 89-98 https://doi.org/10.1016/j.ydbio.2007.12.004
  49. Reichert, V. L., Le Hir, H., Jurica, M. S. and Moore, M. J. (2002) 5' exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly. Genes Dev. 16, 2778-2791 https://doi.org/10.1101/gad.1030602

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