Max Planck Research Group of Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany.
Max Planck Research Group of Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany
J Cell Sci. 2018 Feb 14;131(4):jcs202002. doi: 10.1242/jcs.202002.
Stress can be temporary or chronic, and mild or acute. Depending on its extent and severity, cells either alter their metabolism, and adopt a new state, or die. Fluctuations in environmental conditions occur frequently, and such stress disturbs cellular homeostasis, but in general, stresses are reversible and last only a short time. There is increasing evidence that regulation of gene expression in response to temporal stress happens post-transcriptionally in specialized subcellular membrane-less compartments called ribonucleoprotein (RNP) granules. RNP granules assemble through a concentration-dependent liquid-liquid phase separation of RNA-binding proteins that contain low-complexity sequence domains (LCDs). Interestingly, many factors that regulate microRNA (miRNA) biogenesis and alternative splicing are RNA-binding proteins that contain LCDs and localize to stress-induced liquid-like compartments. Consequently, gene silencing through miRNAs and alternative splicing of pre-mRNAs are emerging as crucial post-transcriptional mechanisms that function on a genome-wide scale to regulate the cellular stress response. In this Review, we describe the interplay between these two post-transcriptional processes that occur in liquid-like compartments as an adaptive cellular response to stress.
压力可以是暂时的或慢性的，可以是轻微的或急性的。根据其程度和严重程度，细胞要么改变其代谢，并采用新的状态，要么死亡。环境条件的波动经常发生，这种压力会扰乱细胞的内稳态，但通常情况下，压力是可逆的，只持续很短的时间。越来越多的证据表明，细胞对暂时压力的基因表达调控是在后转录水平上通过专门的无膜细胞器——核糖核蛋白（RNP）颗粒来实现的。RNP 颗粒通过 RNA 结合蛋白的浓度依赖性液-液相分离组装而成，这些蛋白含有低复杂度序列结构域（LCD）。有趣的是，许多调节 microRNA（miRNA）生物发生和选择性剪接的因子是含有 LCD 并定位于应激诱导的液态区室的 RNA 结合蛋白。因此，通过 miRNA 进行基因沉默和 pre-mRNA 的选择性剪接作为一种普遍存在的转录后机制，在细胞应激反应中发挥作用。在这篇综述中，我们描述了这两种在后转录水平上发生在液态区室中的过程之间的相互作用，它们是细胞对压力的适应性反应。
