Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex.
basic_science · Level V
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- Record sourced from PubMed, PMID 23443539.
- Also identified by DOI 10.1038/ncomms2514.
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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.
Medical subject headings
- Microtubule Proteins
- Nerve Tissue Proteins
- Nuclear Proteins
- Protein Biosynthesis
- Protein Phosphatase 2
- Transcription Factors
- Trinucleotide Repeat Expansion