Spt4 selectively regulates the expression of <i>C9orf72</i> sense and antisense mutant transcripts
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- Nicholas J. Kramer
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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- Yari Carlomagno
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Yong-Jie Zhang
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Sandra Almeida
- Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
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- Casey N. Cook
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Tania F. Gendron
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Mercedes Prudencio
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Marka Van Blitterswijk
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Veronique Belzil
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Julien Couthouis
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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- Joseph West Paul
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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- Lindsey D. Goodman
- Department of Biology and Neuroscience Graduate Program, University of Pennsylvania, Philadelphia, PA, USA.
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- Lillian Daughrity
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Jeannie Chew
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Aliesha Garrett
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Luc Pregent
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Karen Jansen-West
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Lilia J. Tabassian
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Rosa Rademakers
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Kevin Boylan
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
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- Neill R. Graff-Radford
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
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- Keith A. Josephs
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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- Joseph E. Parisi
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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- David S. Knopman
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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- Ronald C. Petersen
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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- Bradley F. Boeve
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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- Ning Deng
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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- Yanan Feng
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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- Tzu-Hao Cheng
- Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
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- Dennis W. Dickson
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Stanley N. Cohen
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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- Nancy M. Bonini
- Department of Biology and Neuroscience Graduate Program, University of Pennsylvania, Philadelphia, PA, USA.
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- Christopher D. Link
- Department of Integrative Physiology, University of Colorado, Boulder, CO, USA.
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- Fen-Biao Gao
- Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
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- Leonard Petrucelli
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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- Aaron D. Gitler
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
説明
<jats:title>Targeting three defects with one strategy</jats:title> <jats:p> The neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia are most commonly caused by a mutation in the <jats:italic>C9orf72</jats:italic> gene. The mutation is an expanded hexanucleotide repeat in a noncoding region. The expanded repeat produces sense and antisense RNA transcripts, which accumulate in patient cells and appear to sequester RNA-binding proteins. The sense and antisense transcripts are also translated into dipeptide repeat proteins, which are aggregation-prone and accumulate in the brain and spinal cord. Last, loss of function from reduced expression of <jats:italic>C9orf72</jats:italic> in neurons and glia could contribute to the disease. Kramer <jats:italic>et al.</jats:italic> targeted both sense and antisense repeats by blocking a single gene called <jats:italic>SPT4</jats:italic> , which mitigated degeneration in human cells by reducing all three types of pathologies. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6300" page="708" related-article-type="in-this-issue" vol="353" xlink:href="10.1126/science.aaf7791">708</jats:related-article> </jats:p>
収録刊行物
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- Science
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Science 353 (6300), 708-712, 2016-08-12
American Association for the Advancement of Science (AAAS)