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.本研究报道，SUMO靶向泛素连接酶（SUMO-targeted ubiquitin ligase, STUbL）Slx5可降低亨廷顿蛋白（huntingtin, htt）突变聚集倾向片段的毒性与异常转录活性，该片段为亨廷顿舞蹈症（HD）的致病因子。额外的SLX5基因拷贝可特异性减少胞质内的htt聚集物，以及细胞核内与染色质结合的htt聚集物。本研究通过RNA测序技术，鉴定并验证了受Slx5调控的突变型htt（mHtt）转录活性特异性靶点。