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A Non-amyloid Prion Particle that Activates a Heritable Gene Expression Program

机译:一种激活遗传基因表达程序的非淀粉样蛋白朊病毒颗粒

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摘要

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.
机译:缺乏折叠的RNA结合结构域外,唾液血基因调节通常由RNA结合蛋白含有长期无序区域。我们认为进化古代发育调节器VTS1 / Smaug的无序区域将自组装驱动成凝胶状凝胶。这些蛋白质颗粒不由淀粉样蛋白组成,但它们是传染性的,使它们作为蛋白质的表观遗传因子:朊病毒[smaug(+)]。与许多淀粉样朊朊病毒朊病毒相比,VTS1的缩合增强其在mRNA衰减中的功能,其自组装性能在大型进化距离上被保守。源细胞涉及[smaug(+)]下调一个密度的相干网络,并在营养限制下表现出改善的生长。由纯化蛋白形成的VTS1缩合物可以将幼稚细胞转化以获得[Smaug(+)]。我们的数据建立了RNA结合蛋白的非淀粉样蛋白自组装可以在染色体之外驱动一种形式的表皮能源,灌输可遗传的基因表达程序,这些计划在长期的生物学尺度上。

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  • 来源
    《Molecular cell》 |2020年第2期|共24页
  • 作者单位

    Stanford Univ Dept Chem &

    Syst Biol 269 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Dept Chem &

    Syst Biol 269 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Dept Biol 269 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Dept Chem &

    Syst Biol 269 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Dept Chem &

    Syst Biol 269 Campus Dr Stanford CA 94305 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
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