Nascent mutant Huntingtin exon 1 chains do not stall on ribosomes during translation but aggregates do recruit machinery involved in ribosome quality control and RNA
Angelique R Ormsby, Dezerae Cox, James Daly, David Priest, Elizabeth Hinde, Danny M Hatters
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2020
Mutations that cause Huntington's Disease involve a polyglutamine (polyQ) sequence expansion beyond 35 repeats in exon 1 of Huntingtin. Intracellular inclusion bodies of mutant Huntingtin protein are a key feature of Huntington's disease brain pathology. We previously showed that in cell culture the formation of inclusions involved the assembly of disordered structures of mHtt exon 1 fragments (Httex1) and they were enriched with translational machinery when first formed. We hypothesized that nascent mutant Httex1 chains co-aggregate during translation by phase separation into liquid-like disordered aggregates and then convert to more rigid, amyloid structures. Here we further examined the m..View full abstract
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Awarded by National Health and Medical Research Council
This work was funded by grants and fellowships from the National Health and Medical Research Council Project to D.M.H. (APP1184166, APP1161803, APP1102059, APP1154352). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.