Abstract
A new mutational basis for human disease was discovered in the beginning of this decade. The genes responsible for fragile X syndrome, spinobulbar muscular atrophy and later the genes causing myotonic dystrophy and Huntington disease were shown to harbor unstable, expanding trinucleotide repeats. The dynamic nature of these mutations explained intriguing features of clinical symptoms observed in families inheriting these diseases. The increasing disease penetrance and expresivity in subsequent family generations could be correlated with the increasing number of trinucleotide repeats. Now, thirteen human hereditary neurological diseases are known to have their underlying cause in the trinucleotide repeat expansions [1] and their list is likely to grow.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Wells, R.D. and Warren, S.T. (1998) Genetic Instabilities and Hereditary Neurological Diseases, Academic Press, San Diego.
Wang, J., Pegoraro, E., Menegazzo, E., Gennarelli, M., Hoop, R.C., Angelini, C., and Hoffman, E.P. (1995) Myotonic dystrophy: evidence for a possible dominant-negative RNA mutation, Hum. Mol. Genet. 4, 599–606.
Korade-Mimics, Z., Babitzke, P., and Hoffman, E.P. (1998) Myotonic dystrophy: molecular windows on a complex etiology, Nucleic Acids Res. 26, 1363–1368.
Philips, A.V., Timchenko, L.T., and Cooper T.A. (1998) Disruption of splicing regulated by a CUGbinding protein in myotonic dystrophy. Science 280, 737–741.
Ohshima, K., Montermini, L., Wells, R.D. and Pandolfo, M. (1998) Inhibitory effects of expanded GAA.TTC triplet repeats from intron I of the Friedreich ataxia gene on transcription and replication in vivo. J Biol. Chem. 273, 14588–14595.
Feng, Y., Zhang, F., Lokey, L.K., Chastain, J.L., Lakkis, L., Eberhart, D., and Warren S.T. (1995) Translational suppression by trinucleotide repeat expansion at FMR1. Science 268, 731–734.
McLaughlin, B.A., Spencer, C., and Eberwine, J. (1996) CAG trinucleotide RNA repeats interact with RNA-binding proteins. Am. J. Hum. Genet. 59, 561–569.
Lunkes, A. and Mandel, J.L. (1997) Polyglutamines, nuclear inclusions and neurodegeneration. Nat Med. 3, 1201–2.
Zuker, M. (1989) On finding all suboptimal foldings of an RNA molecule. Science 244, 48–52.
Timchenko, L.T., Timchenko, N.A., Caskey, C.T., and Roberts, R. (1996) Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy. Hum. Mol. Genet. 5, 115–121.
Timchenko, L.T., Miller, J.W., Timchenko, N.A., DeVore, D.R., Datar, K. V., Lin, L., Roberts, R., Caskey, C.T., and Swanson, M.S. (1996) Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res. 15, 4407–4414.
Bhagwati, S., Ghatpande, A., and Leung, B. (1996) Identification of two nuclear proteins which bind to RNA CUG repeats: significance for myotonic dystrophy. Biochem. Biophys. Res. Commun. 228, 55–62.
Pleiss, J.A., Derrick, M.L., and Uhlenbeck, O.C. (1998) T7 RNA polymerase produces 5’ end heterogeneity during in vitro transcription from certain templates. RNA 4, 1313–1317.
Krzyiosiak, W.J., Denman, R., Nurse, K., Hellmann, W., Boublik, M., Gehrke, C.W., Agris, P.F., and Ofengand, J. (1987) In vitro synthesis of 16S ribosomal RNA containing single base changes and assembly into a functional 30S ribosome. Biochemistry 26, 2353–2364.
Michałowski, D., Wrzesinski, J., and Krzyiosiak, W.J. (1996) Cleavages induced by different metal ions in yeast tRNA(Phe) U59C60 mutants. Biochemistry 35, 10727–10734.
Napierala, M., Michałowski, D., and Krzyżosiak W.J. (1998) in preparation.
Knapp, G. (1989) Enzymatic approaches to probing of RNA secondary and tertiary structure. Methods Enzymol. 180, 192–212.
Jaeger, J.A., SantaLucia, J. Jr, Tinoco, I. Jr. (1993) Determination of RNA structure and thermodynamics. Annu. Rev. Biochem. 62, 255–287.
Ehresmann, C., Baudin, F., Mougel, M., Romby, P., Ebel, J.P., and Ehresmann, B. (1987) Probing the structure of RNAs in solution. Nucleic. Acids Res. 15, 9109–9128.
Krol, A. and Carbon, P. (1989) A guide for probing native small nuclear RNA and ribonucleoprotein structures. Methods Enzymol. 180, 212–227
Brown, R.S., Hingerty, B.E., Dewan, J.C., and Klug, A. (1983) Pb(II)-catalysed cleavage of the sugar-phosphate backbone of yeast tRNAPhe--implications for lead toxicity and self-splicing RNA. Nature 303, 543–546.
Krzyżosiak, W.J., Marciniec, T., Wiewiorowski, M., Romby, P., Ebel, J.P., and Giege, R. (1988) Characterization of the lead(II)-induced cleavages in tRNAs in solution and effect of the Y-base removal in yeast tRNAPhe. Biochemistry 27, 5771–5777.
Ciesiołka, J., Michałowski, D., Wrzesinski, J., Krajewski, J., and Krzyżosiak, W.J. (1998). Patterns of cleavages induced by lead ions in defined RNA secondary structure motifs. J. Mol. Biol. 275, 211–220.
Górnicki, P., Baudin, F., Romby, P., Wiewiórowski, M., Krzyżosiak, W., Ebel, J.P., Ehresmann, C., and Ehresmann, B. (1989) Use of lead(11) to probe the structure of large RNA’s. Conformation of the 3’ terminal domain of E. coli 16S rRNA and its involvement in building the tRNA binding sites. J. Biomol. Struct. Dyn. 6, 971–984.
Brown, R.S., Dewan, J.C., and Klug, A. (1985) Crystallographic and biochemical investigation of the lead(lI)-catalyzed hydrolysis of yeast phenylalanine tRNA. Biochemistry 24, 4785–4801.
Napierala, M. and Krzyżosiak, W.J. (1997) CUG repeats present in myotonin kinase RNA form metastable “slippery” hairpins. J. Biol. Chem. 272, 31079–31085.
Napierala, M., and Krzyżosiak W.J. (1997) unpublished.
Mitas, M., Yu, A., Dill, J., Kamp, T.J., Chambers, E.J., and Haworth, I.S. (1995) Hairpin properties of single-stranded DNA containing a GC-rich triplet repeat: (CTG)15. Nucleic Acids Res. 23, 1050–1059.
Mariappan, S.V., Chen, X., Catasti, P., Bradbury, E.M., and Gupta, G. (1998) Structural Studies on the Unstable Triplet Repeats in R.D. Wells and S.T. Warren (eds.), Genetic Instabilities and Hereditary Neurological Diseases, Academic Press, San Diego, pp. 647–676.
Koch, K.S., Leffert, H.L. (1998) Giant hairpins formed by CUG repeats in myotonic dystrophy messenger RNAs might sterically block RNA export through nuclear pores. J. Theor. Biol. 192, 505–514.
Davis, B.M., McCurrach, M.E., Taneja, K.L., Singer, R.H., annd Housman, D.E. (1997) Expansion of a CUG trinucleotide repeat in the 3’ untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. Proc. Natl. Acad. Sci. USA 94, 7388–7393.
Hamshere, M.G., Newman, E.E., Alwazzan, M., Athwal, B.S., and Brook JD (1997) Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes. Proc. Natl. Acad. Sci. USA 94, 7394–7399.
Klesert, T.R., Otten, A.D., Bird, T.D., and Tapscott, S.J. (1997) Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. Nat. Genet. 16, 402–406.
Thornton, C.A., Wymer, J.P., Simmons, Z., McClain, C., and Moxley, R.T. (1997) Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene. Nat. Genet. 16, 407-409.
Napierala, M., Drozdz, M., Michałowski, D., and Krzyżosiak W.J. (1998) in preparation.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Krzyzosiak, W.J., Napierala, M., Drozdz, M. (1999). RNA Structure Modules with Trinucleotide Repeat Motifs. In: Barciszewski, J., Clark, B.F.C. (eds) RNA Biochemistry and Biotechnology. NATO Science Series, vol 70. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4485-8_22
Download citation
DOI: https://doi.org/10.1007/978-94-011-4485-8_22
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-7923-5862-6
Online ISBN: 978-94-011-4485-8
eBook Packages: Springer Book Archive