SUMO-targeted ubiquitin ligases (STUbLs) reduce the toxicity and abnormal transcriptional activity associated with a mutant, aggregation-prone fragment of huntingtin

We report that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity of a mutant, aggregation-prone fragment of huntingtin (htt), the causative agent of HD. An extra copy of SLX5 specifically reduces htt aggregates in the cytosol as well as chromatin-associated htt aggregates in the nucleus. Using RNA sequencing, we identified and confirmed specific targets of mHtt's transcriptional activity that are modulated by Slx5. Three independent RNA-seq libraries for each of 4 samples were prepared from total RNA of GAL-NLS-25Q-GFP (+/-SLX5) or GAL-NLS-103Q-GFP (+/-SLX5) strains after galactose induction