Structures of CUG repeats in RNA: potential implications for human genetic diseases
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 "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.
fragile-x-syndrome, circular-dichroism spectroscopy, human
hereditary-diseases, single-stranded-dna, ctg triplet repeats, trinucleotide repeat, myotonic-dystrophy, escherichia-coli, in-vitro, conformational-changes
35183-35190
Pinheiro, Philip
dfab395b-12f6-4bab-82d0-5dc0ce6cb299
Scarlett, Garry
1b9c44bf-6713-4338-83d2-c3e6e1bdc19e
Rodger, Alison
af928914-8be9-4009-99ed-20109b3b3d97
Rodger, P. Mark
87999bdc-cc9b-4365-bfa1-bfbd72594243
Murray, Anna
2c3bf35c-26dd-427d-9673-ccbfa7f17e9a
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Newbury, Sarah F.
2f82c60b-fcdc-4190-9217-10a7bbaba73b
McClellan, James A.
dea3e8be-3b4a-4403-ae1d-a63d04ce6597
20 September 2002
Pinheiro, Philip
dfab395b-12f6-4bab-82d0-5dc0ce6cb299
Scarlett, Garry
1b9c44bf-6713-4338-83d2-c3e6e1bdc19e
Rodger, Alison
af928914-8be9-4009-99ed-20109b3b3d97
Rodger, P. Mark
87999bdc-cc9b-4365-bfa1-bfbd72594243
Murray, Anna
2c3bf35c-26dd-427d-9673-ccbfa7f17e9a
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Newbury, Sarah F.
2f82c60b-fcdc-4190-9217-10a7bbaba73b
McClellan, James A.
dea3e8be-3b4a-4403-ae1d-a63d04ce6597
Pinheiro, Philip, Scarlett, Garry, Rodger, Alison, Rodger, P. Mark, Murray, Anna, Brown, Tom, Newbury, Sarah F. and McClellan, James A.
(2002)
Structures of CUG repeats in RNA: potential implications for human genetic diseases.
The Journal of Biological Chemistry, 277 (38), .
(doi:10.1074/jbc.M202235200).
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.
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More information
Published date: 20 September 2002
Keywords:
fragile-x-syndrome, circular-dichroism spectroscopy, human
hereditary-diseases, single-stranded-dna, ctg triplet repeats, trinucleotide repeat, myotonic-dystrophy, escherichia-coli, in-vitro, conformational-changes
Identifiers
Local EPrints ID: 19836
URI: http://eprints.soton.ac.uk/id/eprint/19836
ISSN: 0021-9258
PURE UUID: 22d1f3a9-f9d9-47ae-809f-de263f0bde99
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Date deposited: 22 Feb 2006
Last modified: 15 Mar 2024 06:19
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Contributors
Author:
Philip Pinheiro
Author:
Garry Scarlett
Author:
Alison Rodger
Author:
P. Mark Rodger
Author:
Anna Murray
Author:
Tom Brown
Author:
Sarah F. Newbury
Author:
James A. McClellan
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