The Yeast Prion [SWI(+)] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators Required for Flocculin Gene Expression.
The Yeast Prion [SWI(+)] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators Required for Flocculin Gene Expression.
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DOI：
10.1016/j.celrep.2015.11.060
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发表时间：
2015-12-29
期刊：
影响因子：
8.8
通讯作者：
Li L
中科院分区：
文献类型：
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作者：
Du Z;Zhang Y;Li L
虽然转录因子普遍存在于酵母朊病毒蛋白中，但朊病毒介导的转录调控作用仍然难以捉摸。我们在这里表明，酵母朊病毒[SWI+]消除絮凝蛋白（FLO）基因表达，导致多细胞性完全丧失。进一步的研究表明，除了sw1，其他多种FLO表达必需的蛋白，包括Mss11、Sap30和Msn1也在[SWI+]细胞中发生构象变化，并失去活性。此外，Mss11富含天冬酰胺的区域可以在[SWI+]细胞中以朊病毒样聚集体的形式特异性存在，这些细胞具有sds抗性、遗传性和可治愈性，但在与[SWI+]分离后变为亚稳态。因此，我们的发现揭示了朊病毒介导的机制，通过该机制，生物途径中的多个调节因子可以失活。结合[SWI+]细胞对非葡萄糖糖利用的部分功能丧失表型，我们的数据因此表明，朊病毒可以通过多层次调控对不同性状产生不同的影响，从而为朊病毒的生物学作用提供了见解。
While transcription factors are prevalent among yeast prion proteins, the role of prion-mediated transcriptional regulation remains elusive. We show here that the yeast prion [SWI+] abolishes flocculin (FLO) gene expression and results in a complete loss of multicellularity. Further investigation demonstrates that besides Swi1, multiple other proteins essential for FLO expression, including Mss11, Sap30, and Msn1 also undergo conformational changes, and become inactivated in [SWI+] cells. Moreover, the asparagine-rich region of Mss11 can exist as prion-like aggregates specifically in [SWI+] cells, which are SDS-resistant, heritable, and curable, but become metastable after separation from [SWI+]. Our findings thus reveal a prion-mediated mechanism through which multiple regulators in a biological pathway can be inactivated. In combination with the partial loss-of-function phenotypes of [SWI+] cells on non-glucose sugar utilization, our data therefore demonstrate that a prion can influence differently on distinct traits through multi-level regulations, providing insights into the biological roles of prions.