BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD)
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BC200 RNA is a polyadenylated 200 nucleotide primate brain-specific transcript with 80% homology to the left monomer of the human Alu family of repetitive elements. Whether this transcription product contributes anything to normal brain gene function or is a residue of post transcriptional processing of brain heterogeneous nuclear RNA (hnRNA) is uncertain. However, the high abundance, tissue-specific expression and nucleotide sequence characteristics of BC200 RNA suggests that the generation of this small RNA is associated with some brain cell function. Sustained levels of the BC200 RNA transcript may be indicative of a genetically competent and normally functioning cerebral neocortex.
In this investigation, we have measured the abundance of the BC200 RNA transcript in total RNA isolated from 18 temporal neocortices (Brodman area 22) of brains with no pathology and those affected with neurodegenerative disease. Neocortices were examined from 3 neurologically normal brains, 5 non-Alzheimer dernented [NAD; 3 Huntingtons chorea (HC), 1 amyotrophic lateral sclerosis (ALS) and 1 dementia unclassified] and 10 Alzheimer disease (AD) affected brains. Our results indicate a strong BC200 presence in both the normal brains and NAD affected neocortices, but a 70 per cent reduction in BC200 signal strength in AD afflicted brains. These results may be related to the observation that Alzheimer brains exhibit marked deficits in the abundance of neuron-specific DNA transcripts; these deficits are consistent with the idea that AD is characterized by an impairment in the primary generation of brain gene transcription products.
- Chikaraishi, D. 1979. Complexity and cytoplasmic polyadenylated and nonpolyadenylated rat brain ribonucleic acids. Biochemistry 18:3249–3256.
- Milner, R., and Sutcliffe J. G. 1983. Gene expression in rat brain. Nucl. Acids Res. 11:5497–5250.
- Hahn, W., Chaudhari, N., Sikela, J. and Owens, G. 1986. Messenger RNA in the brain. Pages 10–22,in Giuditta, A. (ed.),The Role of RNA and DNA in brain function, Martinus Nijhoff Publishing, Boston.
- Davidson, E. H., and Britten, R. J. 1969. Gene regulation in higher cells: A theory. Science 165:349–357.
- Watson, J., and Sutcliffe, J. G. 1987. Primate brain specific cytoplasmic transcript of the Alu repeat family. Molec. and Cell. Biol. 7:3324–3327.
- McKinnon, R., Shinnick, T. M., and Sutcliffe, J. G. 1980. The neuronal identified element is a cis-acting positive regulator of gene expression. Proc. Natl. Acad. Sci. USA 83:3751–3755.
- Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., and Lerner, R. 1984. Identifier sequences are transcribed specifically in brain. Nature 308:237–241.
- Britten, R. J., Baron, W., Stout, D. B., and Davidson, E. H. 1988. Sources and evolution of human Alu repeated sequences. Proc. Nat. Acad. Sci. USA 85:4770–4774.
- Jurka, J., and Smith, T. 1988. A tundamental division in the Alu family of repeated sequences. Proc. Natl. Acad. Sci. USA 85:4775–4778.
- Matera, A. G., Hellmann, U., and Schmid, C. W. 1990. A transpositionally and transcriptionally competent Alu subfamily. Molec. and Cell. Biol. 10:5424–5432.
- Allan, M., and Paul, J. 1984. Transcription in vivo of a Alu family member 5′ to the human E-globin gene. Nucl. Acids Res. 12:1193–1200.
- Crapper McLachlan, D. R., Lewis, P. N., Lukiw, W. J., Sima, A., Bergeron, C., and De Boni, U. 1984. Chromatin structure in dementia. Ann. Neurol. 15:329–334.
- Bachelard, H. S., Hodder, V. E., and Walker, A. P. 1986. DNA damage and repair in Alzheimer's disease. Mod. Trends Aging Res. 147:451–458.
- Guillemette, J. G., Wong, L., Crapper McLachlan, D. R., and Lewis, P. N. 1986. Characterization of messenger RNA from the cerebral cortex of control and Alzheimer afflicted brain. J. Neurochem. 47:987–997.
- Kittur, S., Hoh, J., Kawas, C., Tourtellotte, W., Markesbury, W., and Adler, W. 1990. Neurofilament gene expression in Alzheimer's disease. Abstract 135. Second International Conference on Alzheimer's Disease. Neurobiology of Aging 11:285–286.
- Clark, A. W., Krekoski, C. A., and Parhad, I. 1989. Altered expression of genes for amyloid and cytoskeletal proteins in Alzheimer cortex. Ann. Neurol., 25:331–339.
- Crapper McLachlan, D. R., Lukiw, W. J., Wong, L., Bergeron, C., and Bech-Hansen, N. T. 1988. Selective messenger RNA reduction in Alzheimer's disease. Mol. Brain Res. 3:255–262.
- Lukiw, W. J., Wong, L., and McLachlan, D. R. 1990. Cytoskeletal messenger RNA stability in human neocortex: studies in normal aging and in Alzheimer's disease. Intern. J. Neuroscience 55:81–88.
- Taylor, G. R., Carte, G. I., Grow, T. J., Johnson, T. J., Fairbairn, J. A., Perry, E. K. and Perry, R. H. 1986. Recovery and measurement of specific RNA species from postmortem brain tissue: A general reduction in Alzheimer's disease detected by molecular hybridization. Exptl. and Molec. Pathol. 44:111–116.
- Thomas, P. S., 1980. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. USA 77:5201–5205.
- Schmid, C. W., and Jelinek, W. R. 1982. The Alu family of dispersed repetitive sequences. Science 216:1065–1070.
- Feinberg, A. P., and Vogelstein, B. 1983. A technique for labeling DNA restriction fragments to high specific activity. Anal. Biochem. 132:6–13.
- Bains, W. B. 1986. Multiple origins of human Alu sequence. J. Mol. Evolution 23:189–199.
- Lazarides, E. 1982. Intermediate filaments. Ann. Rev. Biochem. 51:219–250.
- Kaplan, B. B., Gioio, A. E., Capano, C. P., and Giuditta, A. 1986. A comparative study of the diversity of gene expression in brain. Pages 1–9in Giuditta, A., (ed.),The Role of RNA and DNA in brain function, Martinus Nijhoff Publishing, Boston.
- Julien, J. P., Grosveld, F., Yazdanbaksh, K., Flavell, D., Meijer, D., and Mushynski, W. 1987. The structure of a human neuro-filament gene (NF-L); a unique exon-intron organization in the intermediate filament gene family. Biochim. et Biophysica Acta. 909:10–20.
- Mattei, M. G., Dautigny, A., Pham-Dinh, D., Passage, E., Mattei, J., and Jolles P. 1988. The gene encoding the large human neurofilament subunit (NF-H) maps to the q121-q131 region on human chromosome 22. Hum. Genet. 80:293–295.
- Chin, S. S. M., and Liem, R. K. 1987. Neurofilaments: A review and an update. In G. Perry, Alterations in The Neuronal Cytoskeleton in Alzheimer's Disease, Advances in Behavioral Biology Vol. 34. Plenum Press, New York.
- Ullu, E. 1982. The human Alu family of repeated DNA sequences. Trends in Biochemical Sciences 82:216–219.
- BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD)
Volume 17, Issue 6 , pp 591-597
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