Abstract
Because molecular oxygen is essential for generating cellular energy in aerobic organisms, and because survival depends on this fundamental requirement for oxygen, all higher organisms have evolved numerous diversely regulated mechanisms to detect and respond to potentially life-threatening occurrences of decreased oxygen availability (hypoxia). While the oxygen-dependent regulation of gene expression involves both transcriptional- and post-transcriptional mechanisms, investigations have focused mainly on mechanisms working at the transcriptional level. In this review, the focus is on a growing body of work that looks at post-transcriptional mechanisms acting at a level of mRNA stability.
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Bruckner, B.A., Ammini, C.V., Otal, M.P., Raizada, M.K., and Stacpoole, P.W., 1999, Regulation of brain glucose transporters by glucose and oxygen deprivation. Metabolism. 48:422–431.
Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C, Declercq, C., Pawling, J., Moons, L., Collen, D., Risau, W., and Nagy, A., 1996, Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 380:435–439.
Claffey, K.P., Shih, S.C., Mullen, A., Dziennis, S., Cusick, J.L., Abrams, K.R., Lee, S.W., and Detmar, M., 1998, Identification of a human VPF/VEGF 3’ untranslated region mediating hypoxia-induced mRNA stability. Mol. Biol. Cell. 9:469–481.
Czyzyk-Krzeska, M.F., Furnari, B.A., Lawson, E.E., and Millhorn, D.E., 1994a, Hypoxia increases rate of transcription and stability of tyrosine hydroxylase mRNA in pheochromocytoma (PC12) cells. J. Biol. Chem. 269:760–764.
Czyzyk-Krzeska, M.F., Dominski, Z., Kole, R., and Millhorn, D.E., 1994b, Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3’-untranslated region of rat tyrosine hydroxylase mRNA. J. Biol. Client. 269:9940–9945.
Czyzyk-Krzeska, M.F., and Beresh, J.E., 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.
Czyzyk-Krzeska, M.F., Paulding, W.R., Beresh, J.E., and Kroll, S.L., 1997, Post-transcriptional regulation of tyrosine hydroxylase gene expression by oxygen in PC 12 cells. Kidney Int. 51:585–590.
Czyzyk-Krzeska, M.F., and Bendixen, A.C., 1999, Identification of the poly(C) binding protein in the complex associated with the 3’ untranslated region of crythropoietin messenger RNA. Blood. 93:2111–2120.
Dibbens, J.A., Miller, D.L., Damert, A., Risau, W., Vadas, M.A., and Goodall, G.J., 1999, Hypoxic Regulation of Vascular Endothelial Growth Factor mRNA Stability Requires the Cooperation of Multiple RNA Elements. Mol. Biol. Cell. 10:907–919.
Ferrara, N., Carver-Moore, K., Chen, H., Dowd. M., Lu, L., O’Shea, K.S., Powell-Braxton, L., Hillan, K.J., and Marme, M.W., 1996, Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 380:439–442.
Finkenzeller, G., Technau, A., and Marine, D., 1995, Hypoxia-induccd transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor, Biochem. Biophys. Res. Commun. 208:432–439.
Fossom, L.H., Sterling, C.R., and Tank, A.W., 1992, Regulation of tyrosine hydroxylase gene transcription rate and tyrosine hydroxylase mRNA stability by cyclic AMP and glucocorticoid. Mol. Pharmacol. 42:898–908.
Folkman, J., and Shing, Y., 1992, Angiogenesis. J. Biol. Chem. 267:10931–10934.
Gamarnik, A.V., and Audio, R., 1997, Two functional complexes formed by KH domain containing proteins with the 5’ noncoding region of poliovirus RNA. RNA. 3:882–892.
Gnarra, J.R., Zhou, S., Merill, M.J., Wagner, J.R., Krumm, A., Papavassiliou, E., Oldfield, E.H., Klausner, R.D., and Linchan, W.M., 1996, Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc. Natl. Acad. Sci. 93:10589–10594.
Goldberg, M.A., Gaut, C.C., and Bunn, H.F., 1991, Erythropoietin mRNA levels are governed by both the rate of gene transcription and posttranscriptional events. Blood. 77:271–277.
Hanson, E.S., Foot, E.M., and Leibold, E.A., 1999, Hypoxia post-translationally activates iron-regulatory protein 2. J. Biol. Chem. 274:5047–5052.
Ho, V., Acquaviva, A., Duh, E., and Bunn, H. F., 1995, Use of a marked erythropoietin gene for investigation of its cis-acting elements. J. Biol. Chem. 270:1084–10090.
Holcik, M., and Liebhaber, S.A., 1997, Four highly stable eukaryotic mRNAs assemble 3’ untranslated region RNA-protein complexes sharing cis and trans components. Proc. Natl. Acad. Sci. 94:2410–2414.
Ikeda, E., Achen, M.G., Breier, G., and Risau, W., 1995, Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J. Biol. Chem. 270:19761–19766.
Iliopoulos, O., Levy, A.P., Jiang, C., Kaelin, W.G. Jr., and Goldberg, M.A., 1996, Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein, Proc. Natl. Acad. Sci. 93:10595–10599.
Jackson, R.M., Parish, G., and Ho, Y.S., 1996, Effects of hypoxia on expression of superoxide dismutases incultured ATII cells and lung fibroblasts. Am. J. Physiol. 271:L955–62.
Kiledjian, M., Wang, X., and Liebhaber, S.A., 1995, Identification of two KH domain proteins in the alpha-globin mRNP stability complex. EMRO. 14:4357–4364.
Latif F., Tory, K., Gnarra, J., Yao, M., Duh, F-M., Orcutt, M.L., Stackhouse, T., Kuzmin, I., Modi, W., Geil, L, Schmidt, L., Zhou, F., Li, H., Wei, M.H., Chen, F., Glenn, G., Choyke, P., Walther, M.M., Weng, Y., Duan, D-S., Dean, M., Glavac, D., Richards, F.M., Crossey, P.A., Ferguson-Smith, M.A., Le Paslier, D., Chumakov, I., Cohen, D., Chinault, A.C., Maher, E.R., Linehun, W.M., Zbar, B., and Lerman, M.I., 1993, Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 260:1317–1320.
Lee, S., Neumann, M., Stearman, R., Stauber, R., Pause, A., Pavlakis, G.N., and Klausner, R.D., 1999, Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein. Mol. Cell. Biol. 19:1486–1497.
Levy, A.P., Levy, N.S., Wegner, S., and Goldberg, M.A., 1995, Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J. Biol. Chem. 270:13333–13340.
Levy, A.P., Levy, N.S., and Goldberg, M.A., 1996a, Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J. Biol. Chem. 271:2746–2753.
Levy, A.P., Levy, N.S., and Goldberg, M.A., 1996b, Hypoxia-inducible protein binding to vascular endothelial growth factor mRNA and its modulation by the von Hippel-Lindau protein. J. Biol. Chem. 271:25492–25497.
Levy, N.S., Goldberg, M.A., and Levy, A.P., 1997, Sequencing of the human vascular endothelial growth factor (VEGF) 3’ untranslated region (UTR): conservation of five hypoxia-inducible RNA-protein binding sites. Biochim. Biophys. Acta. 1352:167–173.
Levy, N.S., Chung, S., Furneaux, H., and Levy, A.P., 1998, Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J. Biol. Chem. 273:6417–6423.
Los, M., Aarsman, C.J., Terpstra, L., Wittebol-Post, D., Lips, C.J., Blijham, G.H., and Voest, E.E., 1997, Elevated ocular levels of vascular endothelial growth factor in patients with von Hippel-Lindau disease. Ann. Oncol. 8:1015–1022.
Maurer, J.A., and Wray, S., 1997, Neuronal dopamine subpopulations maintained in hypothalamic slice explant cultures exhibit distinct tyrosine hydroxylase mRNA turnover rates. J. Neurosci. 17:4552–4561.
Maxwell, P., Wiesener, M.S., Chang, G-W., Clifford, S.C., Vaux, E.C., Cockman, M.E., Wykoff, C.C., Pugh, C.W., Maher, E.R., and Ratcliffe, P.J., 1999, The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 399:271–275.
McGary, E.C., Rondon, I.J., and Beckman, B.S., 1997, Post-transcriptional regulation of erythropoietin mRNA stability by erythropoietin mRNA-binding protein. J. Biol. Chem. 272:8628–8634.
McQuillan, L.P., Leung, G.K., Marsden, P.A., Kostyk, S.K., and Kourembanas, S., 1994, Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am. J. Physiol. 267:H1921–7.
Paulding, W.R., and Czyzyk-Krzeska, M.F., 1999, Regulation of tyrosinc hydroxylase mRNA stability by protein-binding, pyrimidine-rich sequence in the 3’-untranslated region. J. Biol. Client. 274:2532–2538.
Pinsky, D.J., Liao, H., Lawson, C.A., Van, S.F., Chen, J., Carmeliet, P., Loskutoff, D.J., and Stern, D.M., 1998, Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J. Clin. Invest. 102:919–928.
Plate, K.H., Breier, G., and Risau, W., 1994, Molecular mechanisms of developmental and tumor angiogenesis. Brain Pathol. 4:207–218.
Rondon, I.J., MacMillan, L.A., Beckman, B.S., Goldberg, M.A., Schneider, T., Bunn, H.F., and Malter, J.S., 1991, Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein. J. Biol. Chem. 266:16594–16598.
Scandurro, A.B., Rondon, I.J., Wilson, R.B., Tenenbaum, S.A., Carry, R.F., and Beckman, B.S., 1997, Interaction of erythropoietin RNA binding protein with erythropoietin RNA requires an association with heat shock protein 70. Kidney Int. 51:579–584.
Shih, S.C., and Claffey, K.P., 1999, Regulation of human vascular endothelial growth factor mRNA stability in hypoxia by heterogeneous nuclear ribonucleoprotein L. J. Biol. Chem. 274:1359–1365.
Shima, D.T., Deutsch, U., and D’Amore, P.A., 1995, Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability. FEBS Lett. 370:203–208.
Shweiki, D., Itin, A., Soffer, D., and Keshet, E., 1992, Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 359:843–845.
Siemeister, G., Weindel, K., Mohrs, K., Barleon, B., Martiny-Baron, G., and Marme, D., 1996, Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Lindau tumor suppressor protein. Cancer Res. 56:2299–2301.
Stein, I., Neeman, M., Shweiki, D., Itin, A., and Keshet, E., 1995, Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes. Mol. Cell Biol. 15:5363–5368.
Stratmann, R., Krieg, M., Haas, R., and Plate, K.H., 1995, Putative control of angiogenesis in hemangioblastomas by the von Hippel-Lindau tumor suppressor gene. J Neuropathol. Exp. Neurol. 56:1242–1252.
Summerhill, E.M., Wood, K., and Fishman, M.C., Shweiki, 1987, Regulation of tyrosine hydroxylase gene expression during differentiation of neuroblastoma cells, Brain Res.
Vyas, S., Faucon Biguet, N., and Mallet, J., 1990, Transcriptional and post-transcriptional regulation of tyrosine hydroxylase gene by protein kinase C. EMBO. 9:3707–3712.
Wang, X., Kiledjian, M., Weiss, I.M., and Liebhaber, S.A., 1995, Detection and characterization of a 3’ untranslated region ribonucleoprotein complex associated with huma alpha-globin mRNA stability. Mol. Cell. Biol. 15:1769–1777.
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Paulding, W.R., Czyzyk-Krzeska, M.F. (2002). Hypoxia-Induced Regulation of mRNA Stability. In: Lahiri, S., Prabhakar, N.R., Forster, R.E. (eds) Oxygen Sensing. Advances in Experimental Medicine and Biology, vol 475. Springer, Boston, MA. https://doi.org/10.1007/0-306-46825-5_11
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DOI: https://doi.org/10.1007/0-306-46825-5_11
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