RNA 缓冲朊样 RNA 结合蛋白的液-液相分离行为。
RNA buffers the phase separation behavior of prion-like RNA binding proteins.
机构信息
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
出版信息
Science. 2018 May 25;360(6391):918-921. doi: 10.1126/science.aar7366. Epub 2018 Apr 12.
Prion-like RNA binding proteins (RBPs) such as TDP43 and FUS are largely soluble in the nucleus but form solid pathological aggregates when mislocalized to the cytoplasm. What keeps these proteins soluble in the nucleus and promotes aggregation in the cytoplasm is still unknown. We report here that RNA critically regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote phase separation into liquid droplets, whereas high ratios prevent droplet formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA binding causes excessive phase separation and the formation of cytotoxic solid-like assemblies in cells. We propose that the nucleus is a buffered system in which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA binding abilities of RBPs cause aberrant phase transitions.
类朊病毒 RNA 结合蛋白（RBPs），如 TDP43 和 FUS，在细胞核中主要是可溶性的，但当错误定位到细胞质中时，它们会形成固态的病理性聚集体。那么是什么使这些蛋白质在细胞核中保持可溶性并促进在细胞质中聚集，目前尚不清楚。我们在这里报告称，RNA 可显著调控类朊病毒 RBPs 的相分离行为。低 RNA/蛋白比例可促进相分离形成液滴，而高比例则阻止体外液滴的形成。核内 RNA 水平降低或 RNA 结合的基因缺失会导致过度相分离，并在细胞中形成细胞毒性的固态聚集物。我们提出，细胞核是一个缓冲系统，其中高浓度的 RNA 使 RBPs 保持可溶性。RNA 水平或 RBPs 的 RNA 结合能力的变化会导致异常的相变。
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