Abstract
Tau, a neuronal microtuble-associated protein (MAP) plays an important role in the formation and maintenance of neuronal polarity. Tau mRNA is a stable message and exhibits a relatively long half-life in neuronal cells. The regulation of mRNA stability is a crucial determinant in controlling mRNA steady-state levels in neuronal cells and thereby influences gene expression. The half-lives of specific mRNAs may be dependent on specific sequences located at their 3′untranslated region (UTR), which in turn, may be recognized by tissue-specific proteins.
To identify the sequence elements involved in tau mRNA stabilization, selected regions of the 3′UTR were subcloned downstream to c-fos reporter mRNA or to the coding region of the tau mRNA. Using stably transfected neuronal cells, we have demonstrated that a fragment of 240 bp (H fragment) located in the 3′UTR can stabilize c-fos and tau mRNAs. Analysis of stably transfected cells indicated that the transfected tau mRNAs are associated with the microtubules of neuronal cells, suggesting that this association may play a role in tau mRNA stabilization. This step may be a prerequisite in the multistep process leading to the subcellular localization of tau mRNA in neuronal cells.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Alonso A. D. C., Grundke-Iqbal I., Barra H. S., and Iqbal K. (1997) Abnormal phosphorylation of tau and mechanism of Alzheimer neurofibrillary degeneration: Sequestering of MAP1 and 2 and the dissasembly of microtubules by the abnormal tau.Proc. Natl. Acad. Sci. USA 94, 298–303.
Amara F. M., Chen F. Y., and Wright J. A. (1994) Phorobol ester modulation of a novel cytoplasmic protein binding activity at the 3′-untranslated region of mammalian ribonucleotie reductase R2 mRNA and role in message stability.J. Biol. Chem. 269, 6709–6715.
Antic D. and Keen J. D. (1998) Messenger ribonucleoprotein complexes containing human ELAV proteins: interactions with cytoskeleton and translational apparatus.J. Cell Sci. 111, 183–197.
Aranda G. E., Behar L., Chung S., Furneaux H., and Ginzburg I. (1999) Embryonic lethal abnormal vision-like RNA-binding proteins regulate neurite outgrowth and tau expression in PC12 cells.J. Neurosci. 19, in press.
Aviv H., Voloch Z., Bastos R., and Levy S. (1976) Biosynthesis and stability of globine mRNA in cultured erthroleukemic friend cells.Cell 8, 495–503.
Bancher C., Brunner C., Lassmann H., Budka H., Jellinger K., Wiche G., et al. (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer’s disease.Brain Res. 447, 90–99.
Bartel D. P., Sheng M., Lau L. F., and Greenberg M. E. (1989) Growth factors and membrane depolarization activate distinct programs of early response gene expression: dissociation of fos and jun induction.Genes Dev. 3, 304–313.
Bassell G. and Singer R. H. (1997) mRNA and cytoskeletal filaments.Curr. Opinion Cell Biol. 9, 109–115.
Beelman C. A. and Parker R. (1995) Degradation of mRNA in eukaryotes.Cell 81, 179–183.
Behar L., Marx R., Sadot E., Barg J., and Ginzburg I. (1995) Cis-acting signals and trans-acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells.Int. J. Dev. Neurosci. 13, 113–127.
Black M. M. and Baas P. W. (1989) The basis of polarity in neurons.Trends Neurosci. 12, 211–214.
Bogucka-Glotzer J. and Ephrussi A. (1996) mRA localization and the cyoskeleton.Cell Dev. Biol. 7, 357–365.
Brewer G. (1991) An A+U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro.Mol. Cell. Biol. 11, 2460–2466.
Burgin K. E., Waxham M. N., Rickling S., Westgate S. A., Mobley W. C., and Kelly P. T. (1990) In situ hybridization histochemistry of Ca2+/calmodulin-dependent protein kinase in developing rat brain.J. Neurosci. 10, 1788–1798.
Caceres A. and Kosik S. (1990) Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons.Nature 343, 461–463.
Casey J. L., Koeller D. M., Ramin V. C., Klausner R. D., and Harford J. B. (1989) Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3′ untranslated region of the mRNA.EMBO J. 8, 3693–3699.
Chen C.-Y.A. and Shyu A.-B. (1995) AU-rich elements: characterization and importance in mRNA degradation.TIBS 20, 465–470.
Chung S., Perrone-Bizzozero N., Kohn D. T., and Furneaux H. (1997) The Elav-like proteins bind to a conserved regulatory element in the 3′UTR of GAP-43 mRNA.J. Biol. Chem. 272, 6593–6598.
Crosby S. D., Puetz J. J., Simburger K. S., Fahrner T. J., and Milbrandr J. (1991) The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family.Mol. Cell. Biol. 11, 3835–3841.
Curran T. and Morgan J. I. (1985) Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines.Science 229, 1265–1268.
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.
D’arcangelo G. and Halegoua S. (1993) A branched sighaling pathway for nerve growth factor is revealed by src-, ras-, and raf-mediated gene inductions.Mol. Cell Biol. 13, 3146–3155.
Dobashi Y., Mitsuhiko S., Wakata Y., and Kameya T. (1998) Expression of HuD protein is essential for initial ohase of neuronal differentiation in PC12 cells.Biochem. Biophys. Res. Commun. 244, 226–229.
Drubin D. G., Kobayashi S., Kellog D., and Kirschner M. W. (1988) Regulation of microtubule protein levels during cellular morphogenesis in nerve growth-factor treated PC12 cells.J. Cell Biol. 106, 1583–1591.
Fan X. C. and Steitz J. A. (1998) Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs.EMBO J. 17, 3448–3460.
Gao F.-B. (1998) Messenger RNAs in dendrites: localization, stability, and implications for neuronal function.BioEssays 20, 70–78.
Goedert M., Sisodia S. S., and Price D. L. (1991) Neurofibrillary tangles and b-amyloid deposits in Alzheimer’s Disease.Curr. Opinion Neurobiol. 1, 441–447.
Good P. (1997) The role of elav-like genes, a conserved family encoding RNA-binding proteins, in growth and development.Semin. Cell Dev. Biol. 8, 557–584.
Greenberg M. E. and Ziff E. B. (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene.Nature 311, 433–438.
Greene L. A. and Tischler A. (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.Proc. Natl. Acad. Sci. USA 73, 2424–2428.
Grima B., Lamouroux A., Blanot F., Biguet N. F., and Mallet J. (1985) Complete coding sequence of rat tyrosine hydroxylase mRNA.Proc. Natl. Acad. Sci. USA 82, 617–621.
Haby C., Lisovoski F., Aunis D., and Zwiller J. (1994) Stimulation of the cyclic GMP pathway bo NO induces expression of the immediate early genes c-fos and junB in PC12 cells.J. Neurochem. 62, 496–501.
Hamalainen L. O., Karinen J., and Kivirikko K. (1985) Synthesis and degradation of type 1 procollagen mRNA in cultured human skin fibroblasts and the effect of cortisol.J. Biol. Chem. 260, 720–726.
Holcik M. and Liebhaber S. A. (1997) Four highly stable eukaryotic mRNAs assemble 3′untranslated region RNA-protein complexes sharing cis and trans components.Dev. Biol. 94, 2410–2414.
Ikenaka K., Nakahira K., Takayama C., Wada K., Hatanaka H., and Mikosiba K. (1990) Nerve growth factor rapidly induces expression of the 68-kDa neurofilament gene by posttranscriptional modification in PC12h-R cells.J. Biol. Chem. 265, 19,782–19,785.
Jackson R. J. (1993) Cytoplasmic regulation of mRNA function: the importance of the 3′ untranslated region.Cell 74, 9–14.
Jacobson A. and Peltz S. W. (1996) Interrelationships of the pathway of mRNA decay and translation in eukariotic cells.Ann. Rev. Biochem. 65, 693–739.
Jain R. G., Andrews L. G., McGowan K. M., Pekala P. H., and Keene J. D. (1997) Ectopic expression of Hel-N1, an RNA binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes.Mol. Cell. Biol. 17, 954–962.
Khatoon S., Grundek-Iqbal I., and Iqbal K. (1992) Brain levels of mircotubule-associated protein tau are elevated in Alzheimer’s disease: a radioimmunoslot-blot assay for nanograms of the protein.J. Neurochem. 59, 750–753.
Kohn D. T., Tsai K.-C., Cansino V. V., Neve R. L., and Perrone-Bizzozero N. I. (1996) Role of highly conserved pyrimidine-rich sequences in the 3′ untranslated region of the GAP-43 mRNA in mRNA stability and RNA-protein interactions.Mol. Brain Res. 36, 240–250.
Kosik K. S., Orecchio L. D., Bakalis S., and Neve R. L. (1989) Developmentally regulated expression of specific tau sequences.Neuron 2, 1389–1397.
Kosik K. S. (1994) The Alzheimer’s disease Sphinx: A riddle with plaques and tangles.J. Cell Biol. 127, 1501–1504.
Kosik K. S. (1997)Brain Microtubule Associated Protein (Avila J., Brandt R., and Kosik K. S., eds.), Academic, Harwood, pp. 43–52.
Leibold E. A. and Munro H. N. (1988) Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5′ untranslated region of ferritin heavy- and light-subunit mRNAs.PNAS 85, 2171–2175.
Li X. A. and Beebe P. C. (1990) Messenger RNA stabilization in chicken lens development: a re-examination.Dev. Biol. 146, 239–241.
Litman P., Barg J., Rindzoonski L., and Ginzburg I. (1993) Subcellular localization of tau mRNA in differentiating neuronal cell culture: implications for neuronal polarity.Neuron 10, 627–638.
Litman P., Barg J., and Ginzburg I. (1994) Microtubules are involved in the localization of tau mRNA in primary neuronal cell culture.Neuron 13, 1463–1474.
Lodish H. F. and Small B. (1976) Different life times of reticulocyte messenger RNA.Cell 7, 59–69.
Lopresti P., Poluha W., Poluha D. K., Drinkwater E., and Ross A. H. (1992) Neuronal differentiation triggered by blocking cell proliferation.Cell Growth Differ. 3, 627–635.
Maatta a., Ekholm E., and Penttinen R. P. (1995) Effect of the 3′ untranslated region on the expression level and mRNA stability of a1 (1) collagen gene.Biochim. Biophys. Acta 1260, 294–300.
Mangin G., Couchie D., Charriere-Bertrand C., and Nunez J. (1989) Timing of expression of t and its encoding mRNAs in the developing cerebral neocortex and cerebellum of the mouse.J. Neurochem. 53, 45–50.
Parker R. and Jacobson A. (1990) Translation of a 42-nucleotide segment within the coding region of the mRNA encoded by the MATa1 gene are involved in promoting rapid mRNA decay in yeast.Proc. Natl. Acad. Sci. USA 87, 2780–2784.
Peng S. S., Chen C. Y., Xu N., and Shyu A. B. (1998) RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein.EMBO J. 17, 3461–3470.
Rajagopalan L. E., Westmark C. J., Jarzembowski J. A., and Malter J. S. (1998) hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA.Nucleic Acids Res. 26, 3418–3423.
Sadot E., Marx R., Barg J., Behar L., and Ginzburg I. (1994) Complete sequence of 3′-untranslated region of tau from rat central nervous system.J. Mol. Biol. 241, 325–331.
Sadot E., Barg J., Rasouly D., Lazarovici P., and Ginzburg I. (1995) Short- and long-term mechanisms of tau regulation in PC12 cells.J. Cell Sci. 108, 2857–2864.
Sadot E., Heicklen-Klein A., Barg J., Lazarovici P., and Ginzburg I. (1996) Identification of a tau promoter region mediating tissue-specific-regulated expression in PC12 cells.J. Mol. Biol. 256, 805–812.
Sambrook J., Fritsch E. F., and Maniatis T. (1989)Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
Shyu A.-B., Belasco J. G., and Greenberg M. E. (1991) Two distinct destbilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay.Gene Dev. 5, 221–231.
St. Johnston D. (1995) The intracellular localization of messenger RNAs.Cell 81, 161–170.
Tsai K.-C., Cansino V. V., Kohn D. T., Neve R. L., and Perrone-Bizzozero N. I. (1997) Post-transcriptional regulation of the GAP-43 gene by specific sequences in the 3′ UTR of the mRNA.J. Neurosci. 17, 1950–1958.
Wang S., Browning K. S., and Miller W. A. (1996) A viral sequence in the 3′-untranslated region mimics a 5′ cap in facilitating translation of uncapped mRNA.EMBO J. 16, 4107–4116.
Wang X. and Leibhaber S. A. (1996) Complementary change in cis determinants and trans factors in the evolution of an mRNA stability complex.EMBO J. 15, 5040–5051.
Weiss I. M. and Liebhaber S. A. (1994) Erythroid cell-specific determinants of a-globin mRNA stability.Mol. Cell. Biol. 14, 8123–8132.
Wisdom R. and 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.
Yang Q., McDermott P. J., Duzic E., Pleij W. A., Sherlock J. D., and Lanier S. M. (1997) The 3′-untranslated region of the a2c-adrenergic receptor mRNA impedes translation of the receptor of the receptor message.J. Biol. Chem. 272, 15,466–15,473.
Zaidi S. H. E. and Malter J. S. (1994) Amyloid precursor protein mRNA stability is controlled by a-29 base element in the 3′-untranslated region.J. Biol. Chem. 269, 24,007–24,013.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Aronov, S., Marx, R. & Ginzburg, I. Identification of 3′UTR region implicated in tau mRNA stabilization in neuronal cells. J Mol Neurosci 12, 131–145 (1999). https://doi.org/10.1007/BF02736927
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02736927