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首页> 外文期刊>Journal of Molecular Biology >Tah1, A Key Component of R2TP Complex that Regulates Assembly of snoRNP, is Involved in De Novo Generation and Maintenance of Yeast Prion [URE3]
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Tah1, A Key Component of R2TP Complex that Regulates Assembly of snoRNP, is Involved in De Novo Generation and Maintenance of Yeast Prion [URE3]

机译：Tah1是调节Snornp组装的R2TP复合物的关键组成部分，参与了酵母朊病毒的义目和维持[Ure3]

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The cellular chaperone machinery plays key role in the de novo formation and propagation of yeast prions (infectious protein). Though the role of Hsp70s in the prion maintenance is well studied, how Hsp90 chaperone machinery affects yeast prions remains unclear. In the current study, we examined the role of Hsp90 and its co-chaperones on yeast prions [PSI+] and [URE3]. We show that the overproduction of Hsp90 co-chaperone Tah1, cures [URE3] which is a prion form of native protein Ure2 in yeast. The Hsp90 co-chaperone Tah1 is involved in the assembly of small nucleolar ribonucleoproteins (snoRNP) and chromatin remodelling complexes. We found that Tah1 deletion improves the frequency of de novo appearance of [URE3]. The Tah1 was found to interact with Hsp70. The lack of Tah1 not only represses antagonizing effect of Ssa1 Hsp70 on [URE3] but also improves the prion strength suggesting role of Tah1 in both fibril growth and replication. We show that the N-terminal tetratricopeptide repeat domain of Tah1 is indispensable for [URE3] curing. Tah1 interacts with Ure2, improves its solubility in [URE3] strains, and affects the kinetics of Ure2 fibrillation in vitro. Its inhibitory role on Ure2 fibrillation is proposed to influence [URE3] propagation. The present study shows a novel role of Tah1 in yeast prion propagation, and that Hsp90 not only promotes its role in ribosomal RNA processing but also in the prion maintenance.
机译：细胞伴侣机制在酵母朊病毒（感染性蛋白）的从头形成和繁殖中起着关键作用。虽然HSP70在朊病毒维持中的作用已被充分研究，但Hsp90伴侣机制如何影响酵母朊病毒仍不清楚。在目前的研究中，我们检测了Hsp90及其辅伴侣对酵母朊病毒[PSI+]和[URE3]的作用。我们发现，Hsp90辅伴侣Tah1的过量产生治愈了[URE3]，这是酵母中天然蛋白Ure2的一种朊病毒形式。Hsp90辅伴侣Tah1参与小核仁核糖核蛋白（snoRNP）和染色质重塑复合物的组装。我们发现Tah1缺失提高了[URE3]从头出现的频率。发现Tah1与Hsp70相互作用。Tah1的缺乏不仅抑制了Ssa1 Hsp70对[URE3]的拮抗作用，而且还提高了朊病毒的强度，表明Tah1在原纤维生长和复制中的作用。我们发现Tah1的N端四三肽重复结构域对于[URE3]固化是必不可少的。Tah1与Ure2相互作用，提高其在[URE3]菌株中的溶解度，并在体外影响Ure2纤颤的动力学。它对尿素2纤颤的抑制作用被认为会影响[URE3]的传播。目前的研究表明Tah1在酵母朊病毒繁殖中发挥了新的作用，Hsp90不仅促进了其在核糖体RNA加工中的作用，还促进了朊病毒的维持。

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