Polyglutamine (polyQ) repeats shrink and expand. PolyQ expansion over a certain threshold is associated with several neurodegenerative diseases, but the consequences of moderate repeat variations and their physiological role are unclear. PolyQ repeats are found in eukaryotic transcription regulator genes; by generating multiple repeat variants (with normal and excessive lengths) of the yeast transcription factor Ssn6, followed by transcriptome sequencing, Gemayel et al. found that repeat length affects the expression levels of Ssn6 target genes. Analysis of the Ssn6 interactome indicated that repeat length regulates Ssn6 solubility and functional protein interactions. Moreover, Ssn6 with repeats over a certain length had the tendency to misfold and aggregate, which is typical of polyQ-containing proteins; the Hsp70 chaperone Ssa2 was found to reduce aggregation.
References
Gemayel, T. et al. Variable glutamine-rich repeats modulate transcription factor activity. Mol. Cell http://dx.doi.org/10.1016/j.molcel.2015.07.003 (2015)
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Baumann, K. PolyQ repeats regulate transcription. Nat Rev Mol Cell Biol 16, 518 (2015). https://doi.org/10.1038/nrm4055
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DOI: https://doi.org/10.1038/nrm4055