Regulation of G-Protein Coupled Receptor Cytosolic mRNA Binding Proteins

  • Kathryn Sandberg
  • Zheng Wu
  • Hong Ji
  • Eric Hernandez
  • Susan E. Mulroney
Part of the Endocrine Updates book series (ENDO, volume 16)

Abstract

The regulation of G-protein coupled receptor (GPCR) expression is an area of intense interest because GPCRs play a crucial role in many key physiological and pathological processes. Indeed, greater than 60% of all pharmaceuticals are targeted towards GPCRs. The ability to regulate GPCR protein expression at the post-transcriptional level provides a mechanism past the transcriptional regulatory point when genes are turned on or off. This allows a finer control of expression for the GPCRs that are critically involved in a myriad of critical cell functions such as growth, differentiation, and development. In the majority of instances of post-transcriptional regulation, the binding of specific proteins to defined sequences and/or structures in the target mRNA, governs splicing, nucleocytoplasmic transport, subcellular localization, translation and mRNA degradation. In this chapter, we focus on the regulation of GPCRs via cytosolic RNA binding proteins that, through interaction with specific sequences or structures in the mRNA, contribute to determining the level of protein expression by altering the rate of mRNA translation or its stability. Highlighted are our studies on RNA binding proteins that interact with the 5’ leader sequence of the angiotensin AT1 receptor, a GPCR that is critical to the control of blood pressure and fluid homeostasis.

Keywords

mRNA Stability Receptor mRNA Homeostatic Regulation Cell BioI mRNA Decay Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Parola AL, Kobilka BK. 1994. The peptide product of a 5’ leader cistron in the ß2 adrenergic receptor mRNA inhibits receptor synthesis. J. Biol. Chem. 269: 4497–4505.Google Scholar
  2. 2.
    Hadcock JR, Wang HY, Malbon CC. 1989. Agonist-induced destabilization of betaadrenergic receptor mRNA. Attenuation of glucocorticoid-induced up-regulation of betaadrenergic receptors. J. Biol. Chem. 264: 19928–33.Google Scholar
  3. 3.
    Port JD, Huang LY, Malbon CC. 1992. Beta-adrenergic agonists that down-regulate receptor mRNA up-regulate a M(r) 35,000 protein(s) that selectively binds to betaadrenergic receptor mRNAs. J. Biol. Chem. 267: 24103–24108.Google Scholar
  4. 4.
    Theil EC. 1994. Iron regulatory elements (IREs): a family of mRNA non-coding sequences. Biochem. J. 304: 1–11.PubMedGoogle Scholar
  5. 5.
    Yen TJ, Gay DA, Pachter JS, Cleveland DW. 1988. Autoregulated changes in stability of polyribosome-bound beta-tubulin mRNAs are specified by the first 13 translated nucleotides. Mol. Cell Biol. 8: 1224–1235.Google Scholar
  6. 6.
    Chen CY, You Y, Shyu AB. 1992. cellular proteins bind specifically to a purine-rich sequence necessary for the destabilization function of a c-fos protein-coding region determinant of mRNA instability. Mol. Cell Biol. 12: 5748–5757.Google Scholar
  7. 7.
    Bernstein PL, Herrick DJ, Prokipcak RD, Ross J. 1992. Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant. Genes Dev. 6: 642–654.PubMedCrossRefGoogle Scholar
  8. 8.
    Shaw G, Kamen R. 1986. A conserved AU sequence from the 3’ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46: 659–667.PubMedCrossRefGoogle Scholar
  9. 9.
    Shyu AB, Belasco JG, Greenberg ME. 1991. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. Genes Dev. 5: 221–231.PubMedCrossRefGoogle Scholar
  10. 10.
    Wisdom R, Lee W. 1991. The protein-coding region of c-myc mRNA contains a sequence that specifies rapid mRNA turnover and induction by protein synthesis inhibitors. Genes Dev. 5: 232–243.PubMedCrossRefGoogle Scholar
  11. 11.
    Ji H, Wu Z, Lee S, Zheng W, Verbalis JG, Sandberg K. 2000. Translational control in regulation of the renin angiotensin system. Comp. Biochem. Physiol. 126A (suppl 1): 132a.Google Scholar
  12. 12.
    Xu K, Murphy TJ. 2000. Reconstitution of angiotensin receptor mRNA down-regulation in vascular smooth muscle. Post-transcriptional control by protein kinase a but not mitogenic signaling directed by the 5’-untranslated region. J. Biol. Chem. 275: 76047611.Google Scholar
  13. 13.
    Spirin AS, 1996. Masked and translatable messenger ribonucleoprotein in higher eukaryotes. In Translational Control. J.W.B. Hershey, M.B. Mathews, N. Sonenberg, eds., Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 319–334.Google Scholar
  14. 14.
    Kozak M. 1989. The scanning model for translation: an update. J. Cell Biol. 108: 229241.Google Scholar
  15. 15.
    Standart N, Jackson RJ. 1994. Regulation of translation by specific protein/mRNA interactions. Biochimie. 76: 867–79.PubMedCrossRefGoogle Scholar
  16. 16.
    Kozak M. 1989. Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems. Mol. Cell Biol. 9: 5073–5080.PubMedGoogle Scholar
  17. 17.
    Kozak M. 1991. A short leader sequence impairs the fidelity of initiation by eukaryotic ribosomes. Gene Expr. 1: 111–115.PubMedGoogle Scholar
  18. 18.
    Geballe AP, 2000. Translational control by upstream open reading frames. In Translation Control. N. Sonenberg, J.W.B. Hershey, M.B. Mathews, eds., Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 595–614.Google Scholar
  19. 19.
    Mondino A, Jenkins MK. 1995. Accumulation of sequence-specific RNA-binding proteins in the cytosol of activated T cells undergoing RNA degradation and apoptosis. J. Biol. Chem. 270: 26593–26601.Google Scholar
  20. 20.
    Cao J, Geballe AP. 1996. Coding sequence-dependent ribosomal arrest at termination of translation. Mol. Cell Biol. 16: 603–608.Google Scholar
  21. 21.
    Adam SA, Nakagawa T, Swanson MS, Woodruff TK, Dreyfuss G. 1986. mRNA polyadenylate-binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence. Mol. Cell Biol. 6: 2932–2943.Google Scholar
  22. 22.
    Rouault TA, Hentze MW, Haile DJ, Harford JB, Klausner RD. 1989. The iron-responsive element binding protein: a method for the affinity purification of a regulatory RNA-binding protein. Proc. Natl. Acad. Sci. U. S. A. 86: 5768–5772.Google Scholar
  23. 23.
    Klausner RD, Rouault TA, Harford JB. 1993. Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 72: 19–28.PubMedCrossRefGoogle Scholar
  24. 24.
    Gray NK, Hentze MW. 1994. Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs. EMBO J. 13: 38823891.Google Scholar
  25. 25.
    Zuker M. 1989. Computer prediction of RNA structure. Methods Enzymol. 180: 262–288.PubMedCrossRefGoogle Scholar
  26. 26.
    Kozak M. 1991. An analysis of vertebrate mRNA sequences: intimations of translational control. J. Cell Biol. 115: 887–903.PubMedCrossRefGoogle Scholar
  27. 27.
    Krishnamurthi K, Zheng W, Verbalis AD, Sandberg K. 1998. Regulation of cytosolic proteins binding cis elements in the 5’ leader sequence of the angiotensin AT1 receptor mRNA. Biochem. Biophys. Res. Commun. 245: 865–870.Google Scholar
  28. 28.
    Krishnamurthi K, Verbalis JG, Zheng W, Wu Z, Clerch LB, Sandberg K. 1999. Estrogen regulates angiotensin ATI receptor expression via cytosolic proteins that bind to the 5’ leader sequence of the receptor mRNA. Endocrinology 140: 5431–5434.CrossRefGoogle Scholar
  29. 29.
    Kozak M. 1987. An analysis of 5’-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 26: 8125–8148.CrossRefGoogle Scholar
  30. 30.
    Kozak M. 1999. Initiation of translation in prokaryotes and eukaryotes. Gene 234: 187208.Google Scholar
  31. 31.
    Sonenberg N, Hershey JWB, Mathews MB, 2000. Translational control of gene expression. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.Google Scholar
  32. 32.
    Fleurent M, Gingras AC, Sonenberg N, Meloche S. 1997. Angiotensin II stimulates phosphorylation of the translational repressor 4E-binding protein 1 by a mitogenactivated protein kinase-independent mechanism. J. Biol. Chem. 272: 4006–4012.Google Scholar
  33. 33.
    McCarthy JE, Kollmus H. 1995. Cytoplasmic mRNA-protein interactions in eukaryotic gene expression. Trends Biochem. Sci. 20: 191–197.Google Scholar
  34. 34.
    Hinnebusch AG. 1994. Translational control of GCN4: an in vivo barometer of initationfactor activity. Trends Biochem. Sci. 19: 409–414.Google Scholar
  35. 35.
    Sandberg K. 1994. Structural analysis and regulation of angiotensin II receptors. Trends Endo. Metab. 5: 28–35.Google Scholar
  36. 36.
    Wu Z, Aguilera G, Zheng W, Sandberg K. 2000. Adrenalectomy regulates corticotropinreleasing factor receptor expression by regulating mRNA binding proteins (New Orleans, RNA Society 5th Annual Meeting), pp. 708.Google Scholar
  37. 37.
    Herrick DJ, Ross J. 1994. The half-life of c-myc mRNA in growing and serum-stimulated cells: influence of the coding and 3’ untranslated regions and role of ribosome translocation. Mol. Cell Biol. 14: 2119–2128.Google Scholar
  38. 38.
    Prokipcak RD, Herrick DJ, Ross J. 1994. Purification and properties of a protein that binds to the C-terminal coding region of human c-myc mRNA. J. Biol. Chem. 269: 92619269.Google Scholar
  39. 39.
    Gay DA, Sisodia SS, Cleveland DW. 1989. Autoregulatory control of beta-tubulin mRNA stability is linked to translation elongation. Proc. Natl. Acad. Sci. U. S. A. 86: 5763–5767.Google Scholar
  40. 40.
    Pachter JS, Yen TJ, Cleveland DW. 1987. Autoregulation of tubulin expression is achieved through specific degradation of polysomal tubulin mRNAs. Cell 51: 283–292.PubMedCrossRefGoogle Scholar
  41. 41.
    Schiavi SC, Wellington CL, Shyu AB, Chen CY, Greenberg ME, Belasco JG. 1994. Multiple elements in the c-fos protein-coding region facilitate mRNA deadenylation and decay by a mechanism coupled to translation. J. Biol. Chem. 269: 3441–3448.Google Scholar
  42. 42.
    Shyu AB, Greenberg ME, Belasco JG. 1989. The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev. 3: 60–72.PubMedCrossRefGoogle Scholar
  43. 43.
    Lu DL, Menon KM. 1996. 3’ untranslated region-mediated regulation of luteinizing hormone/human chorionic gonadotropin receptor expression. Biochemistry 35: 123471 2353.Google Scholar
  44. 44.
    Hoffman YM, Peegel H, Sprock MJ, Zhang QY, Menon KM. 1991. Evidence that human chorionic gonadotropin/luteinizing hormone receptor down-regulation involves decreased levels of receptor messenger ribonucleic acid. Endocrinology 128: 388–393.PubMedCrossRefGoogle Scholar
  45. 45.
    Lu DL, Peegel H, Mosier SM, Menon KM. 1993. Loss of lutropin/human choriogonadotropin receptor messenger ribonucleic acid during ligand-induced down-regulation occurs post transcriptionally. Endocrinology 132: 235–240.PubMedCrossRefGoogle Scholar
  46. 46.
    Kash JC, Menon KMJ. 1998. Identification of a hormonally regulated luteinizing hormone/human chorionic gonadotropin receptor mRNA binding protein. J. Biol. Chem. 273: 10658–10664.Google Scholar
  47. 47.
    Kash JC, Menon KM. 1999. Sequence-specific binding of a hormonally regulated mRNA binding protein to cytidine-rich sequences in the lutropin receptor open reading frame. Biochemistry 38: 16889–16897.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang H, Ascoli M, Segaloff DL. 1991. Multiple luteinizing hormone/chorionic gonadotropin receptor messenger ribonucleic acid transcripts. Endocrinology 129: 133138.Google Scholar
  49. 49.
    Koo YB, Ji I, Slaughter RG, Ji TH. 1991. Structure of the luteinizing hormone receptor gene and multiple exons of the coding sequence. Endocrinology 128: 2297–2308.PubMedCrossRefGoogle Scholar
  50. 50.
    Hu ZZ, Buczko E, Zhuang L, Dufau ML. 1994. Sequence of the 3’-noncoding region of the luteinizing hormone receptor gene and identification of two polyadenylation domains that generate the major mRNA forms. Biochim. Biophys. Acta. 1220: 333–337.Google Scholar
  51. 51.
    Weiss IM, Liebhaber SA. 1995. Erythroid cell-specific mRNA stability elements in the alpha 2-globin 3’ nontranslated region. Mol. Cell Biol. 15: 2457–2465.Google Scholar
  52. 52.
    Holcik M, Liebhaber SA. 1997. Four highly stable eukaryotic mRNAs assemble 3’ untranslated region RNA- protein complexes sharing cis and trans components. Proc. Natl. Acad. Sci. U. S.A. 94: 2410–2414.Google Scholar
  53. 53.
    Kiledjian M, Wang X, Liebhaber SA. 1995. Identification of two KH domain proteins in the alpha-globin mRNP stability complex. EMBO. J. 14: 4357–4364.Google Scholar
  54. 54.
    Kiledjian M, DeMaria CT, Brewer G, Novick K. 1997. Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the alpha-globin mRNA stability complex. Mol. Cell Biol. 17: 4870–4876.Google Scholar
  55. 55.
    Czyzyk-Krzeska MF, Dominski, Z., Kole, R. and D.E. Millhorn. 1994. Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3’untranslated region of rat tyrosine hydroxylase mRNA. J. Biol. Chem. 269: 9940–9945.Google Scholar
  56. 56.
    Czyzyk-Krzeska MF, Beresh JE. 1996. Characterization of the hypoxia-inducible protein binding site within the pyrimidine-rich tract in the 3’-untranslated region of the tyrosine hydroxylase mRNA. J. Biol. Chem. 271: 3293–3299.Google Scholar
  57. 57.
    Paulding WR, Czyzyk-Krzeska MF. 1999. Regulation of tyrosine hydroxylase mRNA stability by protein-binding, pyrimidine-rich sequence in the 3’-untranslated region. J. Biol. Chem. 274: 2532–2538.Google Scholar
  58. 58.
    Carter BZ, Malter JS. 1991. Regulation of mRNA stability and its relevance to disease. Lab. Invest. 65: 610–621.Google Scholar
  59. 59.
    Peltz SW, Brewer G, Bernstein P, Hart PA, Ross J. 1991. Regulation of mRNA turnover in eukaryotic cells. Crit. Rev. Eukaryot. Gene Expr. 1: 99–126.Google Scholar
  60. 60.
    Hargrove JL, Schmidt FH. 1989. The role of mRNA and protein stability in gene expression. Faseb J. 3: 2360–2370.PubMedGoogle Scholar
  61. 61.
    Hargrove JL. 1993. Microcomputer-assisted kinetic modeling of mammalian gene expression. Faseb J. 7: 1163–1170.PubMedGoogle Scholar
  62. 62.
    Bernstein P, Ross J. 1989. Poly(A), poly(A) binding protein and the regulation of mRNA stability. Trends Biochem. Sci. 14: 373–377.Google Scholar
  63. 63.
    Bernstein P, Peltz SW, Ross J. 1989. The poly(A)-poly(A)-binding protein complex is a major determinant of mRNA stability in vitro. Mol. Cell Biol. 9: 659–670.Google Scholar
  64. 64.
    Peltz SW, Jacobson A. 1992. mRNA stability: in trans-it. Curr. Opin. Cell Biol. 4: 979983.Google Scholar
  65. 65.
    Burd CG, Dreyfuss G. 1994. Conserved structures and diversity of functions of RNA-binding proteins. Science 265: 615–621.PubMedCrossRefGoogle Scholar
  66. 66.
    Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A. 1986. Identification of a common nucleotide sequence in the 3’-untranslated region of mRNA molecules specifying inflammatory mediators. Proc. Natl. Acad. Sci. U. S. A. 83: 16701674.Google Scholar
  67. 67.
    Chen CY, Shyu AB. 1995. AU-rich elements: characterization and importance in mRNA degradation Trends Biochem. Sci. 20: 465–470.Google Scholar
  68. 68.
    Pandey NB, Williams AS, Sun JH, Brown VD, Bond U, Marzluff WF. 1994. Point mutations in the stem-loop at the 3’ end of mouse histone mRNA reduce expression by reducing the efficiency of 3’ end formation. Mol. Cell Biol. 14: 1709–1720.Google Scholar
  69. 69.
    Chen FY, Amara FM, Wright JA. 1993. Mammalian ribonucleotide reductase R1 mRNA stability under normal and phorbol ester stimulating conditions: involvement of a cis-trans interaction at the 3’ untranslated region. EMBO J. 12: 3977–3986.PubMedGoogle Scholar
  70. 70.
    Amara FM, Chen FY, Wright JA. 1993. A novel transforming growth factor-beta 1 responsive cytoplasmic trans-acting factor binds selectively to the 3’-untranslated region of mammalian ribonucleotide reductase R2 mRNA: role in message stability. Nucleic Acids Res. 21: 4803–4809.PubMedCrossRefGoogle Scholar
  71. 71.
    Zhang W, Wagner BJ, Ehrenman K, Schaefer AW, DeMaria CT, Crater D, DeHaven K, Long L, Brewer G. 1993. Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1. Mol. Cell Biol. 13: 7652–7665.Google Scholar
  72. 72.
    Blaxall BC, Pellett AC, Wu SC, Pende A, Port JD. 2000. Purification and characterization of beta-adrenergic receptor mRNA- binding proteins. J. Biol. Chem. 275: 4290–4297.Google Scholar
  73. 73.
    Mitchusson KD, Blaxall BC, Pende A, Port JD. 1998. Agonist-mediated destabilization of human betal-adrenergic receptor mRNA: role of the 3’ untranslated translated region. Biochem. Biophys. Res. Commun. 252: 357–362.Google Scholar
  74. 74.
    Pende A, Tremmel KD, DeMaria CT, Blaxall BC, Minobe WA, Sherman JA, Bisognano JD, Bristow MR, Brewer G, Port J. 1996. Regulation of the mRNA-binding protein AUF 1 by activation of the beta-adrenergic receptor signal transduction pathway. J. Biol. Chem. 271: 8493–8501.Google Scholar
  75. 75.
    Tholanikunnel BG, Granneman JG, Malbon CC. 1995. The M(r) 35,000 beta-adrenergic receptor mRNA-binding protein binds transcripts of G-protein-linked receptors which undergo agonist-induced destabilization. J. Biol. Chem. 270: 12787–12793.Google Scholar
  76. 76.
    Nickenig G, Michaelsen F, Muller C, Vogel T, Strehlow K, Bohm M. 2001. Post-transcriptional regulation of the AT1 receptor mRNA. Identification of the mRNA binding motif and functional characterization. Faseb J. 15: 1490–1492.Google Scholar
  77. 77.
    Ross J. 1996. Control of messenger RNA stability in higher eukaryotes. Trends Genet. 12: 171–175.PubMedCrossRefGoogle Scholar
  78. 78.
    Haynes SR. 1999. RNA-protein interaction protocols. In Methods in Molecular Biology. J.M. Walker, ed. Vol 118, Totowa: Humana Press.Google Scholar
  79. 79.
    Smith CWJ. 1998. RNA:Protein Interactions. In The Practical Approach Series. B.D. Hames, ed., Oxford: Oxford University Press.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Kathryn Sandberg
    • 1
  • Zheng Wu
    • 1
  • Hong Ji
    • 1
  • Eric Hernandez
    • 1
  • Susan E. Mulroney
    • 1
  1. 1.Georgetown University School of MedicineUSA

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