A prion accelerates proliferation at the expense of lifespan

Organisms often commit to one of two strategies: living fast and dying young or living slow and dying old. In fluctuating environments, however, switching between these two strategies could be advantageous. Lifespan is often inversely correlated with cell size and proliferation, which are both limited by protein synthesis. Here we report that a highly conserved RNA-modifying enzyme, the pseudouridine synthase Pus4/TruB, can act as a prion, endowing yeast with greater proliferation rates at the cost of a shortened lifespan. Cells harboring the prion can grow larger and exhibit altered protein synthesis. This epigenetic state, [BIG+] (better in growth), allows cells to heritably yet reversibly alter their translational program, leading to the differential expression of hundreds of proteins, including many that regulate proliferation and aging. Our data reveal a functional role for aggregation of RNA-modifying enzymes in driving heritable epigenetic states that transform cell growth and survival.生物体通常会采取两种生存策略之一：要么快速生长、早夭，要么慢速生长、终老。然而在波动环境中，在这两种策略间切换或许具备进化优势。寿命通常与细胞大小及增殖能力呈负相关，而二者均受蛋白质合成过程的限制。本研究发现，一种高度保守的RNA修饰酶——假尿苷合酶（pseudouridine synthase）Pus4/TruB，可作为朊病毒（prion）发挥功能，使酵母（yeast）获得更高的增殖速率，但代价是寿命缩短。携带该朊病毒的细胞体积可增大，并表现出蛋白质合成模式的改变。这种名为[BIG+]（better in growth，即生长更优）的表观遗传状态（epigenetic state），可使细胞以可遗传但可逆的方式改变其翻译程序（translational program），进而导致数百种蛋白质出现差异表达（differential expression），其中包含诸多调控增殖与衰老的蛋白。本研究数据揭示了RNA修饰酶的聚集（aggregation）在驱动可遗传表观遗传状态、重塑细胞生长与存活过程中的功能作用。