DOI: 10.1126/science.1173110. Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA

Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA

10.1126/science.1173110

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Resisting Repeats A set of diseases, including myotonic dystrophy, are caused by the expansion of a simple repeat in genomic DNA, which, when transcribed into RNA, can be toxic to other cellular processes. Ameliorating the effects of this toxic, repeat-laden RNA may also relieve the symptoms of the disease. Wheeler et al. (p. 336 ; see the Perspective by Cooper ) developed an antisense morpholino oligonucleotide complementary to the expanded repeats found in the myotonic dystrophy protein kinase messenger RNA (mRNA). The morpholino bound the repeats in vitro and displaced the inappropriately bound and sequestered RNA splicing factor, Muscleblind-like 1. In an in vivo mouse model for myotonic dystrophy, local injection of the morpholino corrected a number of cellular defects in muscle, including the alternative mRNA splicing of several genes, among them the muscle-specific chloride channel, CIC1, leading to a marked reduction in the myotonia.

Bibliography

Wheeler, T. M., Sobczak, K., Lueck, J. D., Osborne, R. J., Lin, X., Dirksen, R. T., & Thornton, C. A. (2009). Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA. Science, 325(5938), 336â339.

Authors 7

Thurman M. Wheeler (first)
Krzysztof Sobczak (additional)
John D. Lueck (additional)
Robert J. Osborne (additional)
Xiaoyan Lin (additional)
Robert T. Dirksen (additional)
Charles A. Thornton (additional)

References 26 Referenced 344

Dates

Type	When
Created	16 years, 1 month ago (July 16, 2009, 5:47 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 5:03 a.m.)
Indexed	3 weeks, 3 days ago (Aug. 2, 2025, 1 a.m.)
Issued	16 years, 1 month ago (July 17, 2009)
Published	16 years, 1 month ago (July 17, 2009)
Published Print	16 years, 1 month ago (July 17, 2009)

Funders 0

None

BibTeX

@article{Wheeler_2009, title={Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA}, volume={325}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1173110}, DOI={10.1126/science.1173110}, number={5938}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Wheeler, Thurman M. and Sobczak, Krzysztof and Lueck, John D. and Osborne, Robert J. and Lin, Xiaoyan and Dirksen, Robert T. and Thornton, Charles A.}, year={2009}, month=jul, pages={336–339} }

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  "abstract": "<jats:title>Resisting Repeats</jats:title>\n          <jats:p>\n            A set of diseases, including myotonic dystrophy, are caused by the expansion of a simple repeat in genomic DNA, which, when transcribed into RNA, can be toxic to other cellular processes. Ameliorating the effects of this toxic, repeat-laden RNA may also relieve the symptoms of the disease.\n            <jats:bold>\n              Wheeler\n              <jats:italic>et al.</jats:italic>\n            </jats:bold>\n            (p.\n            <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" page=\"336\" related-article-type=\"in-this-issue\" vol=\"325\" xlink:href=\"10.1126/science.1173110\">336</jats:related-article>\n            ; see the Perspective by\n            <jats:bold>\n              <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" issue=\"5938\" page=\"272\" related-article-type=\"in-this-issue\" vol=\"325\" xlink:href=\"10.1126/science.1177452\">Cooper</jats:related-article>\n            </jats:bold>\n            ) developed an antisense morpholino oligonucleotide complementary to the expanded repeats found in the myotonic dystrophy protein kinase messenger RNA (mRNA). The morpholino bound the repeats in vitro and displaced the inappropriately bound and sequestered RNA splicing factor, Muscleblind-like 1. In an in vivo mouse model for myotonic dystrophy, local injection of the morpholino corrected a number of cellular defects in muscle, including the alternative mRNA splicing of several genes, among them the muscle-specific chloride channel, CIC1, leading to a marked reduction in the myotonia.\n          </jats:p>",
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