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, James A. McClellan

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)35183-35190
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number38
DOIs
Publication statusPublished - 20 Sep 2002
Externally publishedYes

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    Pinheiro, P., Scarlett, G., Rodger, A., Mark Rodger, P., Murray, A., Brown, T., ... McClellan, J. A. (2002). Structures of CUG repeats in RNA: potential implications for human genetic diseases. Journal of Biological Chemistry, 277(38), 35183-35190. https://doi.org/10.1074/jbc.M202235200