School of Molecular Sciences, University of Western Australia, Crawley, Western Australia, Australia.
School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia.
Bioessays. 2021 May;43(5):e2000245. doi: 10.1002/bies.202000245. Epub 2021 Mar 22.
Paraspeckles are nuclear condensates, or membranelees organelles, that are built on the long noncoding RNA, NEAT1, and have been linked to many diseases. Although originally described as constitutive structures, here, in reviewing this field, we develop the hypothesis that cells increase paraspeckle abundance as part of a general stress response, to aid pro-survival pathways. Paraspeckles increase in many scenarios: when cells transform from one state to another, become infected with viruses and bacteria, begin to degenerate, under inflammation, in aging, and in cancer. Cells increase paraspeckles by increasing transcription of NEAT1 and adjusting its RNA processing. These increases in NEAT1 are driven by numerous stress-sensing signaling pathways, including signaling to mitochondria and stress granules, revealing crosstalk between the cytoplasm and nucleoplasm in the stress response. Thus, paraspeckles are an important piece of the puzzle in cellular homeostasis, and could be considered RNA-scaffolded nuclear equivalents of dynamic stress-induced structures that form in the cytoplasm. We speculate that, in general, cells rely on phase-separated paraspeckles to transiently tweak gene regulation in times of cellular flux.
核斑点是核内凝聚物或无膜细胞器，它们构建在长链非编码 RNA NEAT1 上，并与许多疾病有关。尽管最初被描述为组成型结构，但在回顾这一领域时，我们提出了这样一种假设，即细胞增加核斑点的丰度是作为一般应激反应的一部分，以帮助生存途径。在许多情况下，核斑点会增加：当细胞从一种状态转变为另一种状态，感染病毒和细菌，开始退化，发生炎症，衰老和癌症时。细胞通过增加 NEAT1 的转录和调整其 RNA 处理来增加核斑点。这些 NEAT1 的增加是由许多应激感应信号通路驱动的，包括向线粒体和应激颗粒的信号传递，揭示了应激反应中细胞质和核质之间的串扰。因此，核斑点是细胞内稳态的重要组成部分，并且可以被认为是细胞质中形成的动态应激诱导结构的 RNA 支架核等效物。我们推测，一般来说，细胞依赖于相分离的核斑点来在细胞流动时暂时调整基因调控。
