Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

Ribosomes are often seen as monolithic machines produced from uniformly regulated genes. However, in yeast most ribosomal proteins come from duplicated genes. Here, we demonstrate that gene duplication may serve as an adaption mechanism modulating the global proteome through the differential expression of ribosomal proteins paralogs after exposure to stress. Our data indicate that the yeast paralog pair of the ribosomal protein L7/uL30 produces two differentially acetylated proteins. Under normal conditions most ribosomes incorporate the hypo-acetylated major form favoring the translation of genes with short open reading frames. Exposure to drugs, on the other hand, increases the production of ribosomes carrying the hyper-acetylated minor paralog that increases translation of long reading frames. Many of these long genes encode cell wall proteins that increase drug resistance in a programed change in translation equilibrium. Together the data reveal a mechanism of translation control through the differential fates of near-identical ribosomal protein isoforms.核糖体(ribosome)通常被视为由受统一调控的基因编码产生的单一体分子机器。然而在酵母中，大多数核糖体蛋白(ribosomal protein)源自重复基因。本研究证实，基因重复可作为一种适应机制：当生物体遭受应激刺激时，通过调控核糖体蛋白旁系同源物(paralog)的差异表达来重塑全局蛋白质组(proteome)。我们的数据显示，酵母中核糖体蛋白L7/uL30的旁系同源基因对，可编码两种经差异乙酰化修饰的蛋白质。正常生理条件下，大多数核糖体会整合低乙酰化的主要亚型，该亚型偏好性翻译带有短开放阅读框(open reading frame, ORF)的基因。反之，当暴露于药物胁迫时，携带高乙酰化次要旁系同源亚型的核糖体生成量增加，这类核糖体则偏好性翻译长开放阅读框基因。这些长开放阅读框基因中有许多编码细胞壁蛋白，它们可通过翻译平衡的程序性改变提升细胞的药物抗性。综合以上所有数据，本研究揭示了一种翻译调控机制：通过近乎完全相同的核糖体蛋白同工型(isoform)的不同命运，实现对翻译过程的精准控制。