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RNA Binding Proteins pp 101–117Cite as

Regulation of mRNA Stability by AUF1

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Part of the book series: Endocrine Updates ((ENDO,volume 16))

Abstract

A+U-rich elements (AREs) are potent cis-acting determinants of rapid cytoplasmic mRNA turnover in mammalian cells. Regulation of mRNA decay rates by these sequences is mediated by interaction with cellular factors. Association of the protein AUF1 with an ARE-containing transcript targets the mRNA for decay, involving the assembly or recruitment of a multi-subunit trans-acting complex. In this chapter, recent evidence is described which indicates that recognition of ARE sequences by AUF1 induces dynamic protein oligomerization, which may serve as a scaffold for association of other cytoplasmic factors leading to catabolism of the RNA substrate. This mechanism of targeted trans-acting complex assembly may be regulated at several points, either involving differential expression of individual subunits or through the activity of selected signal transduction pathways. Finally, specific examples are described where alterations in the distribution of AUF1 isoforms lead to differential gene expression during development, and where accelerated mRNA turnover associated with enhanced AUF1 protein levels may contribute to the pathogenesis of congestive heart failure.

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References

  1. Hargrove, J.L. and F.H. Schmidt. 1989. The role of mRNA and protein stability in gene expression. FASEB J. 3: 2360–2370.

    PubMed  CAS  Google Scholar 

  2. Ross, J. 1995. mRNA stability in mammalian cells. Microbiol. Rev. 59: 423–450.

    Google Scholar 

  3. Chen, C.-Y.A. and A.-B. Shyu. 1995. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem. Sci. 20: 465–470.

    Article  PubMed  CAS  Google Scholar 

  4. Shaw, G. and R. Kamen. 1986. A conserved AU sequence from the 3’ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46: 659–667.

    Article  PubMed  CAS  Google Scholar 

  5. Wilson, T. and R. Treisman. 1988. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3’ AU-rich sequences. Nature 336: 396–399.

    Article  PubMed  CAS  Google Scholar 

  6. Meijlink, F., T. Curran, A.D. Miller, and I.M. Verma. 1985. Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene. Proc. Natl. Acad. Sci. USA 82: 4987–4991.

    Article  PubMed  CAS  Google Scholar 

  7. Zubiaga, A.M., J.G. Belasco, and M.E. Greenberg. 1995. The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation. Mol. Cell. Biol. 15: 2219–2230.

    PubMed  CAS  Google Scholar 

  8. Lagnado, C.A., C.Y. Brown, and G.J. Goodall. 1994. AUUUA is not sufficient to promote poly(A) shortening and degradation of an mRNA: the functional sequence within AU-rich elements may be UUAUUUA(U/A)(U/A). Mol. Cell. Biol. 14: 79847995.

    Google Scholar 

  9. Peng, S.S.Y., C.-Y.A. Chen, and A.-B. Shyu. 1996. Functional characterization of a non-AUUUA AU-rich element from the c-jun proto-oncogene mRNA: evidence for a novel class of AU-rich elements. Mol. Cell. Biol. 16: 1490–1499.

    PubMed  CAS  Google Scholar 

  10. Stoecklin, G., S. Hahn, and C. Moroni. 1994. Functional hierarchy of AUUUA motifs in mediating rapid interleukin-3 mRNA decay. J. Biol. Chem. 269: 28591–28597.

    PubMed  CAS  Google Scholar 

  11. Laroia, G., R. Cuesta, G. Brewer, and R.J. Schneider. 1999. Control of mRNA decay by heat shock-ubiquitin-proteosome pathway. Science 284: 499–502.

    Article  PubMed  CAS  Google Scholar 

  12. Peppel, K., J.M. Vinci, and C. Baglioni. 1991. The AU-rich sequences in the 3’ untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids. J. Exp. Med. 173: 349–355.

    Article  PubMed  CAS  Google Scholar 

  13. Winzen, R., M. Kracht, B. Ritter, A. Wilhem, C.-Y.A. Chen, A.-B. Shyu, M. Muller, M. Gaestel, K. Resch, and H. Holtmann 1999. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18: 4969–4980.

    Article  PubMed  CAS  Google Scholar 

  14. Lasa, M., K.R. Mahtani, A. Finch, G. Brewer, J. Saklatvala, and A.R. Clark. 2000. Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade. Mol. Cell. Biol. 20: 4265–4274.

    Article  PubMed  CAS  Google Scholar 

  15. Ming, X.-F., M. Kaiser, and C. Moroni. 1998. c-jun N-terminal kinase is involved in AUUUA-mediated interleukin-3 mRNA turnover in mast cells. EMBO J. 17: 60396048.

    Google Scholar 

  16. Montero, L. and Y. Nagamine. 1999. Regulation by p38 mitogen-activated protein kinase of adenylate-and uridylate-rich element-mediated urokinase-type plasminogen activator (uPA) messenger RNA stability and uPA-dependent in vitro cell invasion. Cancer Res. 59: 5286–5293.

    PubMed  CAS  Google Scholar 

  17. Xu, K., A.M. Robida, and T.J. Murphy. 2000. Immediate-early MEK-1-dependent stabilization of rat smooth muscle cell cyclooxygenase-2 mRNA by Gag-coupled receptor signaling. J. Biol. Chem. 275: 23012–23019.

    Article  PubMed  CAS  Google Scholar 

  18. Sirenko, O.I., A.K. Lofquist, C.T. DeMaria, J.S. Morris, G. Brewer, and J.S. Haskill. 1997. Adhesion-dependent regulation of an A+U-rich element-binding activity associated with AUF1. Mol. Cell. Biol. 17: 3898–3906.

    PubMed  CAS  Google Scholar 

  19. Wilson, G.M. and G. Brewer. 1999. The search for trans-acting factors controlling messenger RNA decay. Prog. Nucleic Acids Res. Mol. Biol. 62: 257–291.

    Article  CAS  Google Scholar 

  20. Brewer, G. and J. Ross. 1990. Messenger RNA turnover in cell-free extracts. Methods Enzymol. 181: 202–209.

    Article  PubMed  CAS  Google Scholar 

  21. Brewer, G. and J. Ross. 1989. Regulation of c-myc mRNA stability in vitro by a labile destabilizer with an essential nucleic acid component. Mol. Cell. Biol. 9: 1996–2006.

    PubMed  CAS  Google Scholar 

  22. Brewer, G. and J. Ross. 1988. Poly(A) shortening and degradation of the 3’ AU-rich sequences of human c-myc mRNA in a cell-free system. Mol. Cell. Biol. 8: 1697–1708.

    PubMed  CAS  Google Scholar 

  23. Brewer, G. 1991. An A+U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. Mol. Cell. Biol. 11: 2460–2466.

    PubMed  CAS  Google Scholar 

  24. Zhang, W., B.J. Wagner, K. Ehrenman, A.W. Schaefer, C.T. DeMaria, D. Crater, K. DeHaven, L. Long, and G. Brewer. 1993. Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1. Mol. Cell. Biol. 13: 76527665.

    Google Scholar 

  25. Wagner, B.J., C.T. DeMaria, Y. Sun, G.M. Wilson, and G. Brewer. 1998. Structure and genomic organization of the human AUF1 gene: alternative pre-RNA splicing generates four protein isoforms. Genomics 48: 195–202.

    Article  PubMed  CAS  Google Scholar 

  26. Ehrenman, K., L. Long, B.J. Wagner, and G. Brewer. 1994. Characterization of cDNAs encoding the murine A+U-rich RNA-binding protein AUF1. Gene 149: 315319.

    Google Scholar 

  27. Wagner, B.J., L. Long, P.N. Rao, M.J. Pettenati, and G. Brewer. 1996. Localization and physical mapping of genes encoding the A+U-rich element RNA-binding protein AUF1 to human chromosomes 4 and X. Genomics 34: 219–222.

    Article  PubMed  CAS  Google Scholar 

  28. Nagai, K., C. Oubridge, N. Ito, J. Avis, and P. Evans. 1995. The RNP domain: a sequence-specific RNA-binding domain involved in processing and transport of RNA. Trends Biochem.Sci. 20: 235–240.

    Article  PubMed  CAS  Google Scholar 

  29. Oubridge, C., N. Ito, P.R. Evans, C.-H. Teo, and K. Nagai. 1994. Crystal structure at 1.92A resolution of the RNA-binding domain of the U1A spiceosomal protein complexed with an RNA hairpin. Nature 372: 432–438.

    Article  PubMed  CAS  Google Scholar 

  30. Handa, N., O. Nureki, K. Kurimoto, I. Kim, H. Sakamoto, Y. Shimura, Y. Muto, and S. Yokoyama. 1999. Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein. Nature 398: 579–585.

    Article  PubMed  CAS  Google Scholar 

  31. DeMaria, C.T., Y. Sun, L. Long, B.J. Wagner, and G. Brewer. 1997. Structural determinants in AUF1 required for high affinity binding to A+U-rich elements. J. Biol. Chem. 272: 27635–27643.

    Article  PubMed  CAS  Google Scholar 

  32. Arao, Y., R. Kuriyama, F. Kayama, and S. Kato. 2000. A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D. Arch. Biochem. Biophys. 380: 228–236.

    Article  PubMed  CAS  Google Scholar 

  33. Tay, N., S.H. Chan, and E.C. Ren. 1992. Identification and cloning of a novel heterogeneous nuclear ribonucleoprotein C-like protein that functions as a transcriptional activator of the hepatitis B virus enhancer II. J. Virol. 66: 6841–6848.

    PubMed  CAS  Google Scholar 

  34. Kajita, Y., J. Nakayama, M. Aizawa, and F. Ishikawa. 1995. The UUAG-specific RNA-binding protein, heterogeneous nuclear ribonucleoprotein DO. J. Biol. Chem. 270: 22167–22175.

    Article  PubMed  CAS  Google Scholar 

  35. Dempsey, L.A., L.A. Hanakahi, and N. Maizels. 1998. A specific isoform of hnRNP D interacts with DNA in the LR1 heterodimer: canonical RNA binding motifs in a sequence-specific duplex DNA binding protein. J. Biol. Chem. 273: 29224–29229.

    Article  PubMed  CAS  Google Scholar 

  36. Tolnay, M., J.D. Lambris, and G.C. Tsokos. 1997. Transcriptional regulation of the complement receptor 2 gene: role of a heterogeneous nuclear ribonucleoprotein. J. Immunol. 159: 5492–5501.

    PubMed  CAS  Google Scholar 

  37. DeMaria, C.T. and G. Brewer. 1996. AUF1 binding affinity to A+U-rich elements correlates with rapid mRNA degradation. J. Biol. Chem. 271: 12179–12184.

    Article  PubMed  CAS  Google Scholar 

  38. Wilson, G.M., Y. Sun, H. Lu, and G. Brewer. 1999. Assembly of AUF1 oligomers on U-rich RNA targets by sequential dimer association. J. Biol. Chem. 274: 33374–33381.

    Article  PubMed  CAS  Google Scholar 

  39. Körner, C.G. and E. Wahle. 1997. Poly(A) tail shortening by a mammalian poly(A)specific 3’-exoribonuclease. J. Biol. Chem. 272: 10448–10456.

    Article  PubMed  Google Scholar 

  40. Körner, C.G., M. Wormington, M. Muckenthaler, S. Schneider, E. Dehlin, and E. Wahle. 1998. The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. EMBO J. 17: 5427–5437.

    Article  PubMed  Google Scholar 

  41. Dehlin, E., M. Wormington, C.G. Körner, and E. Wahle. 2000. Cap-dependent deadenylation of mRNA. EMBO J. 19: 1079–1086.

    Article  PubMed  CAS  Google Scholar 

  42. Gao, M., D.T. Fritz, L.P. Ford, and J. Wilusz. 2000. Interaction between a poly(A)specific ribonuclease and the 5’ cap influences mRNA deadenylation rates in vitro. Mol. Cell 5: 479–488.

    Article  PubMed  CAS  Google Scholar 

  43. Kiledjian, M., C.T. DeMaria, G. Brewer, and K. Novick. 1997. Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the a-globin mRNA stability complex. Mol. Cell. Biol. 17: 4870–4876.

    PubMed  CAS  Google Scholar 

  44. Haskill, S., C. Johnson, D. Eierman, S. Becker, and K. Warren. 1988. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J. Immunol. 140: 1690–1694.

    PubMed  CAS  Google Scholar 

  45. Sporn, S.A., D.F. Eierman, C.E. Johnson, J. Morris, G. Martin, M. Ladner, and S. Haskill. 1990. Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. J. Immunol. 144: 4434–4441.

    PubMed  CAS  Google Scholar 

  46. Ross, H., N. Sato, Y. Ueyama, and H. Koeffler. 1991. Cytokine messenger RNA stability is enhanced in tumor cells. Blood 77: 1787–1795.

    PubMed  CAS  Google Scholar 

  47. Buzby, J.S., S. Lee, P. van Winkle, C.T. DeMaria, G. Brewer, and M.S. Cairo. 1996. Increased granulocyte-macrophage colony-stimulating factor mRNA instability in cord versus adult mononuclear cells is translation-dependent and associated with increased levels of A+U-rich element binding factor. Blood 88: 2889–2897.

    PubMed  CAS  Google Scholar 

  48. Loflin, P., C.-Y.A. Chen, and A.-B. Shyu. 1999. Unraveling a cytoplasmic role for hnRNP D in the in vivo mRNA destablization directed by the AU-rich element. Genes Dev. 13: 1884–1897.

    Article  PubMed  CAS  Google Scholar 

  49. Cohn, J.N., T.B. Levine, M.T. Olivari, V. Garberg, D. Lura, G.S. Francis, A.B. Simon, and T. Rector. 1984. Plasma norepinepherine as a guide to prognosis in patients with chronic congestive heart failure. N. Engl. J. Med. 311: 819–823.

    Article  PubMed  CAS  Google Scholar 

  50. Bristow, M.R., W. Minobe, R. Rasmussen, P. Larrabee, L. Skerl, J.W. Klein, F.L. Anderson, J. Murray, L. Mestroni, S.W. Karwande, M. Fowler, and R. Ginsburg. 1992. 3-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms. J. Clin. Invest. 89: 803–815.

    Google Scholar 

  51. Bristow, M.R., W.A. Minobe, M.V. Raynolds, J.D. Port, R. Rasmussen, P.E. Ray, and M. Feldman. 1993. Reduced beta 1 receptor messenger RNA abundance in the failing human heart. J. Clin. Invest. 92: 2737–2745.

    Article  PubMed  CAS  Google Scholar 

  52. Hadcock, J.R., H. Wang, and C.C. Malbon. 1989. Agonist-induced destabilization of beta-adrenergic receptor mRNA. Attenuation of glucocorticoid-induced up-regulation of beta-adrenergic receptors. J. Biol. Chem. 264: 19928–19933.

    PubMed  CAS  Google Scholar 

  53. Pende, A., K.D. Tremmel, C.T. DeMaria, B.C. Blaxall, W.A. Minobe, J.A. Sherman, J.D. Bisognano, M.R. Bristow, G. Brewer, and J.D. Port. 1996. Regulation of the mRNA-binding protein AUF1 by activation of the 3-adrenergic receptor signal transduction pathway. J. Biol. Chem. 271: 8493–8501.

    Article  PubMed  CAS  Google Scholar 

  54. English, B.K., W.P. Hammond, D.B. Lewis, C.B. Brown, and C.B. Wilson. 1992. Decreased granulocyte-macrophage colony-stimulating factor production by human neonatal blood mononuclear cells and T cells. Pediatr. Res. 31: 211–216.

    Article  PubMed  CAS  Google Scholar 

  55. Lee, S.M., E. Knoppel, C. van de Ven, and M.S. Cairo. 1993. Transcriptional rates of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3, and macrophage colony-stimulating factor genes in activated cord versus adult mononuclear cells: alteration in cytokine expression may be secondary to posttranscriptional instability. Pediatr. Res. 34: 560–564.

    Article  PubMed  CAS  Google Scholar 

  56. Buzby, J.S., G. Brewer, and D.J. Nugent. 1999. Developmental regulation of RNA transcript destabilization by A+U-rich elements is AUF1-dependent. J. Biol. Chem. 274: 33973–33978.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. UMDNJ, Robert Wood Johnson Medical School, Piscataway, NJ, USA

    Gerald M. Wilson & Gary Brewer

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  1. Gerald M. Wilson
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  2. Gary Brewer
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Editors and Affiliations

  1. Departments of Medicine and Physiology & Biophysics, Georgetown University School of Medicine, Washington, DC, USA

    Kathryn Sandberg Ph.D. (Associate Professor) (Associate Professor)

  2. Department of Physiology & Biophysics, Georgetown University School of Medicine, Washington, DC, USA

    Susan E. Mulroney Ph.D. (Associate Professor) (Associate Professor)

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Wilson, G.M., Brewer, G. (2002). Regulation of mRNA Stability by AUF1. In: Sandberg, K., Mulroney, S.E. (eds) RNA Binding Proteins. Endocrine Updates, vol 16. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-6446-8_6

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  • DOI: https://doi.org/10.1007/978-1-4757-6446-8_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-4935-6

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