Chromatin remodeling regulates gene expression in response to the accumulation of misfolded polyQ proteins associated with Huntington's disease (HD). Tra1 is an essential component of both the SAGA/SLIK and NuA4 transcription co-activator complexes and is linked to multiple cellular processes, including protein trafficking and signaling pathways associated with misfolded protein stress. Cells with compromised Tra1 activity display phenotypes distinct from deletions encoding components of the SAGA and NuA4 complexes, indicating a potentially unique regulatory role of Tra1 in the cellular response to protein misfolding. Here, we employed a yeast model to define how the expression of toxic polyQ expansion proteins affects Tra1 expression and function. Expression of expanded polyQ proteins mimics deletion of SAGA/NuA4 components and results in growth defects under stress conditions. Moreover, deleting genes encoding SAGA and, to a lesser extent, NuA4 components exacerbates polyQ toxicity. Also, cells carrying a mutant Tra1 allele displayed increased sensitivity to polyQ toxicity. Interestingly, expression of polyQ proteins upregulated the expression of TRA1 and other genes encoding SAGA components, revealing a feedback mechanism aimed at maintaining Tra1 and SAGA functional integrity. Moreover, deleting the TORC1 (Target of Rapamycin) effector SFP1 abolished upregulation of TRA1 upon expression of polyQ proteins. While Sfp1 is known to adjust ribosome biogenesis and cell size in response to stress, we identified a new role for Sfp1 in the control of TRA1 expression, linking TORC1 and cell growth regulation to the SAGA acetyltransferase complex during misfolded protein stress.

中文翻译：

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Sfp1将TORC1和细胞生长调节与酵母SAGA复杂成分Tra1关联起来，以响应polyQ蛋白毒性。

染色质重塑调节基因表达，以响应与亨廷顿舞蹈病（HD）相关的错误折叠的polyQ蛋白的积累。Tra1是SAGA / SLIK和NuA4转录共激活因子复合物的重要组成部分，并与多个细胞过程相关，包括蛋白质运输和与错误折叠的蛋白质应激相关的信号传导途径。具有受损的Tra1活性的细胞表现出不同于编码SAGA和NuA4复合物的缺失的表型，表明Tra1在细胞对蛋白质错误折叠的反应中可能具有独特的调节作用。在这里，我们采用了酵母模型来定义毒性polyQ扩展蛋白的表达如何影响Tra1的表达和功能。扩增的polyQ蛋白的表达模拟了SAGA / NuA4组件的缺失，并在应激条件下导致了生长缺陷。此外，删除编码SAGA的基因，以及在较小程度上减少NuA4成分，会加剧polyQ的毒性。同样，携带突变Tra1等位基因的细胞对polyQ毒性显示出更高的敏感性。有趣的是，polyQ蛋白的表达上调了TRA1和其他编码SAGA组件的基因的表达，揭示了旨在维持Tra1和SAGA功能完整性的反馈机制。此外，删除TORC1（雷帕霉素的靶标）效应子SFP1消除了polyQ蛋白表达后TRA1的上调。虽然已知Sfp1可调节核糖体的生物发生和响应压力的细胞大小，但我们发现Sfp1在TRA1表达控制中具有新的作用，