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

Sybille Krauss (Lead / Corresponding author), Nadine Griesche, Ewa Jastrzebska, Changwei Chen, Desiree Rutschow, Clemens Achmuller, Stephanie Dorn, Sylvia M. Boesch, Maciej Lalowski, Erich Wanker, Rainer Schneider, Susann Schweiger (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    41 Citations (Scopus)

    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.
    Original languageEnglish
    Article number1511
    JournalNature Communications
    Volume4
    Early online date26 Feb 2013
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Protein Phosphatase 2
    Protein Biosynthesis
    proteins
    Messenger RNA
    phosphatases
    Ribosomal Protein S6 Kinases
    Proteins
    expansion
    Huntington Disease
    Sirolimus
    Neurodegenerative Diseases
    Up-Regulation
    disorders
    ribonucleic acids
    Therapeutics

    Cite this

    Krauss, S., Griesche, N., Jastrzebska, E., Chen, C., Rutschow, D., Achmuller, C., ... Schweiger, S. (2013). Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex. Nature Communications, 4, [1511]. https://doi.org/10.1038/ncomms2514
    Krauss, Sybille ; Griesche, Nadine ; Jastrzebska, Ewa ; Chen, Changwei ; Rutschow, Desiree ; Achmuller, Clemens ; Dorn, Stephanie ; Boesch, Sylvia M. ; Lalowski, Maciej ; Wanker, Erich ; Schneider, Rainer ; Schweiger, Susann. / Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex. In: Nature Communications. 2013 ; Vol. 4.
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    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.",
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    Krauss, S, Griesche, N, Jastrzebska, E, Chen, C, Rutschow, D, Achmuller, C, Dorn, S, Boesch, SM, Lalowski, M, Wanker, E, Schneider, R & Schweiger, S 2013, 'Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex', Nature Communications, vol. 4, 1511. https://doi.org/10.1038/ncomms2514

    Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex. / Krauss, Sybille (Lead / Corresponding author); Griesche, Nadine; Jastrzebska, Ewa; Chen, Changwei; Rutschow, Desiree; Achmuller, Clemens; Dorn, Stephanie; Boesch, Sylvia M.; Lalowski, Maciej; Wanker, Erich ; Schneider, Rainer; Schweiger, Susann (Lead / Corresponding author).

    In: Nature Communications, Vol. 4, 1511, 2013.

    Research output: Contribution to journalArticle

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    AU - Boesch, Sylvia M.

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    AU - Schweiger, Susann

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