Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex

Sybille Krauß (), Nadine Griesche, Ewa Jastrzebska, Changwei Chen, Désiree Rutschow, Clemens Achmüller, Stephanie Dorn, Sylvia M. Boesch, Maciej Lalowski, Erich Wanker, Rainer Schneider and Susann Schweiger ()
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Sybille Krauß: German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, 53127
Nadine Griesche: German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, 53127
Ewa Jastrzebska: Charité University Hospital
Changwei Chen: Medical Research Institute, Ninewels Hospital & Medical School
Désiree Rutschow: Medical Research Institute, Ninewels Hospital & Medical School
Clemens Achmüller: Institute of Biochemistry and Center for Molecular Biosciences Innsbruck (CMBI)
Stephanie Dorn: German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, 53127
Sylvia M. Boesch: Innsbruck Medical University
Maciej Lalowski: Proteomics and Molecular Mechanisms of Neurodegenerative Diseases, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Erich Wanker: Proteomics and Molecular Mechanisms of Neurodegenerative Diseases, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Rainer Schneider: Max Planck Institute for Molecular Genetics
Susann Schweiger: Max Planck Institute for Molecular Genetics

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington’s disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1–protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A- and mammalian target of rapamycin-dependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-complex may serve as a therapeutic target for the treatment of CAG repeat expansion disorders.

Date: 2013
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DOI: 10.1038/ncomms2514

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