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J. Biol. Chem., Vol. 277, Issue 38, 35183-35190, September 20, 2002

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Structures of CUG Repeats in RNA
POTENTIAL IMPLICATIONS FOR HUMAN GENETIC DISEASES^*

Philip Pinheiro, Garry Scarlett, Alison Rodger^§¶, P. Mark Rodger^§, Anna Murray, Tom Brown^**, Sarah F. Newbury, and James A. McClellan

From the  Biophysics Laboratories, School of Biological Sciences, University of Portsmouth, St. Michael's Building, White Swan Road, Portsmouth, PO1 2DT, United Kingdom, the  Wessex Regional Genetics Laboratory, Salisbury Health Care National Health Service Trust, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, United Kingdom, the ^** Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom, the ^§ Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom, and the  Department of Biochemistry, South Parks Road, Oxford OX1 3QU, United Kingdom

Triplet repeats that cause human genetic diseases have been shown to exhibit unusual compact structures in DNA, and in this paper we show that similar structures exist in shorter "normal length" CNG RNA. CUG and control RNAs were made chemically and by in vitro transcription. We find that "normal" short CUG RNAs migrate anomalously fast on non-denaturing gels, compared with control oligos of similar base composition. By contrast, longer tracts approaching clinically relevant lengths appear to form higher order structures. The CD spectrum of shorter tracts is similar to triplex and pseudoknot nucleic acid structures and different from classical hairpin spectra. A model is outlined that enables the base stacking features of poly(r(G-C))₂·poly(r(U)) or poly(d(G-C))₂·poly(d(T)) triplexes to be achieved, even by a single 15-mer.

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