mRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the 5’ to 3’ exonuclease Xrn1. Here we show that nucleocytoplasmic shuttling of several yeast mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1, location of one of which is conserved from yeast to human. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Preventing Xrn1 import, either by deleting KAP120 or mutating the two Xrn1 NLSs, compromises transcription and, unexpectedly, also cytoplasmic decay, uncovering a cytoplasmic decay pathway that initiates in the nucleus. Most mRNAs are degraded by both pathways - the ratio between them represents a full spectrum. Importantly, Xrn1 shuttling is required for proper responses to environmental changes, e.g., fluctuating temperatures, involving proper changes in mRNA abundance and in cell proliferation rate.

mRNA 水平受介导 mRNA 合成和衰变的因素控制，包括 5' 至 3' 核酸外切酶 Xrn1。在这里，我们表明几种酵母 mRNA 衰变因子的核质穿梭在确定 mRNA 合成和衰变中起着关键作用。穿梭受核转运蛋白 Kap120 与 Xrn1 中两个核定位序列 (NLS) 的 RNA 控制结合的调节，其中一个核定位序列的位置从酵母到人类都是保守的。腐烂的 RNA 结合并掩盖 NLS1，从而在 mRNA 衰变和 Xrn1 穿梭之间建立联系。通过删除KAP120防止 Xrn1 导入或突变两个 Xrn1 NLS，会损害转录，并且出乎意料地还会损害细胞质衰变，从而揭示在细胞核中启动的细胞质衰变途径。大多数 mRNA 都会被这两种途径降解——它们之间的比率代表了一个完整的范围。重要的是，Xrn1 穿梭是对环境变化做出适当反应所必需的，例如，温度波动，涉及 mRNA 丰度和细胞增殖率的适当变化。