Spatiotemporal gene regulation is often driven by RNA-binding proteins that harbor long intrinsically disordered regions in addition to folded RNA-binding domains. We report that the disordered region of the evolutionarily ancient developmental regulator Vts1/Smaug drives self-assembly into gel-like condensates. These proteinaceous particles are not composed of amyloid, yet they are infectious, allowing them to act as a protein-based epigenetic element: a prion [SMAUG+]. In contrast to many amyloid prions, condensation of Vts1 enhances its function in mRNA decay, and its self-assembly properties are conserved over large evolutionary distances. Yeast cells harboring [SMAUG+] downregulate a coherent network of mRNAs and exhibit improved growth under nutrient limitation. Vts1 condensates formed from purified protein can transform naive cells to acquire [SMAUG+]. Our data establish that non-amyloid self-assembly of RNA-binding proteins can drive a form of epigenetics beyond the chromosome, instilling adaptive gene expression programs that are heritable over long biological timescales.

中文翻译：

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激活可遗传基因表达程序的非淀粉样蛋白朊病毒颗粒。

时空基因调控通常由 RNA 结合蛋白驱动，除了折叠的 RNA 结合域外，这些蛋白还包含长的本质上无序的区域。我们报告说，进化上古老的发育调节器 Vts1/Smaug 的无序区域驱动自组装成凝胶状凝聚物。这些蛋白质颗粒不是由淀粉样蛋白组成，但它们具有传染性，使它们能够充当基于蛋白质的表观遗传元素：朊病毒 [SMAUG+]。与许多淀粉样蛋白朊病毒相反，Vts1 的缩合增强了其在 mRNA 衰变中的功能，并且其自组装特性在较大的进化距离内保持不变。含有 [SMAUG+] 的酵母细胞下调 mRNA 的连贯网络，并在营养限制下表现出改善的生长。由纯化蛋白形成的 Vts1 凝聚物可以转化幼稚细胞以获得 [SMAUG+]。我们的数据表明，RNA 结合蛋白的非淀粉样蛋白自组装可以驱动染色体以外的一种表观遗传学形式，灌输适应性基因表达程序，这些程序可在较长的生物时间尺度上遗传。