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 |
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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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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. 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Potential implications for human genetic diseases</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><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.</description><subject>Base Sequence</subject><subject>Circular Dichroism</subject><subject>DNA Primers</subject><subject>Genetic Diseases, Inborn - genetics</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Nucleic Acid Conformation</subject><subject>Plasmids</subject><subject>RNA - chemistry</subject><subject>RNA - genetics</subject><subject>Transcription, Genetic</subject><subject>Trinucleotide Repeats</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAUhT2AaCmsjMgTW8L1I7U9VhUUpPIQpXPkODfgKi9iZ-DfE4kyc5azfDr6dAi5YpAyUPL2ULj0iQPnIuMAJ2QOwFlieKZn5DyEA0yRhp2RGeOgFOPZnOx2cRhdHAcMtKvoer-hA_ZoY6C-pW_Pq5S-dhHb6G1NfdPX3tnouzbQqhvo59jYln5gi9E7WvqANmC4IKeVrQNeHntB9vd37-uHZPuyeVyvtknPhY7J0mljoTCTScbQgWPagsEqq4DLMhPSqUIqYzgHl4EurSwcU2YphBPWcRQLcvO72w_d14gh5o0PDuvattiNIVccjBCC_QsyLfVy8pjA6yM4Fg2WeT_4xg7f-d9f4gdznmny</recordid><startdate>20020920</startdate><enddate>20020920</enddate><creator>Pinheiro, Philip</creator><creator>Scarlett, Garry</creator><creator>Rodger, Alison</creator><creator>Rodger, P Mark</creator><creator>Murray, Anna</creator><creator>Brown, Tom</creator><creator>Newbury, Sarah F</creator><creator>McClellan, James A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20020920</creationdate><title>Structures of CUG repeats in RNA. 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Potential implications for human genetic diseases</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-09-20</date><risdate>2002</risdate><volume>277</volume><issue>38</issue><spage>35183</spage><epage>35190</epage><pages>35183-35190</pages><issn>0021-9258</issn><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. 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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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