Structures of CUG repeats in RNA. Potential implications for human genetic diseases

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...

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Veröffentlicht in:The Journal of biological chemistry 2002-09, Vol.277 (38), p.35183-35190
Hauptverfasser: Pinheiro, Philip, Scarlett, Garry, Rodger, Alison, Rodger, P Mark, Murray, Anna, Brown, Tom, Newbury, Sarah F, McClellan, James A
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container_end_page 35190
container_issue 38
container_start_page 35183
container_title The Journal of biological chemistry
container_volume 277
creator Pinheiro, Philip
Scarlett, Garry
Rodger, Alison
Rodger, P Mark
Murray, Anna
Brown, Tom
Newbury, Sarah F
McClellan, James A
description 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.
doi_str_mv 10.1074/jbc.M202235200
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subjects Base Sequence
Circular Dichroism
DNA Primers
Genetic Diseases, Inborn - genetics
Humans
Models, Molecular
Nucleic Acid Conformation
Plasmids
RNA - chemistry
RNA - genetics
Transcription, Genetic
Trinucleotide Repeats
title Structures of CUG repeats in RNA. Potential implications for human genetic diseases
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