miRISC is a multi-protein assembly that uses microRNAs (miRNAs) to identify mRNAs targeted for repression. Dozens of miRISC-associated proteins have been identified, and interactions between many factors have been examined in detail. However, the physical nature of the complex remains unknown. Here, we show that two core protein components of human miRISC, Argonaute2 (Ago2) and TNRC6B, condense into phase-separated droplets in vitro and in live cells. Phase separation is promoted by multivalent interactions between the glycine/tryptophan (GW)-rich domain of TNRC6B and three evenly spaced tryptophan-binding pockets in the Ago2 PIWI domain. miRISC droplets formed in vitro recruit deadenylation factors and sequester target RNAs from the bulk solution. The condensation of miRISC is accompanied by accelerated deadenylation of target RNAs bound to Ago2. The combined results may explain how miRISC silences mRNAs of varying size and structure and provide experimental evidence that protein-mediated phase separation can facilitate an RNA processing reaction.

中文翻译：

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人类miRISC的组装和功能中的相变。

miRISC是一种多蛋白装配，使用microRNA（miRNA）来识别靶向阻遏的mRNA。已经鉴定了数十种与miRISC相关的蛋白，并且已经详细研究了许多因素之间的相互作用。但是，该复合物的物理性质仍然未知。在这里，我们显示了人类miRISC的两个核心蛋白成分，Argonaute2（Ago2）和TNRC6B，在体外和活细胞中凝结成相分离的液滴。TNRC6B富含甘氨酸/色氨酸（GW）的域与Ago2 PIWI域中三个均匀间隔的色氨酸结合口袋之间的多价相互作用促进了相分离。体外形成的miRISC小滴可从本体溶液中募集去腺苷酸化因子和螯合靶RNA。miRISC的缩合伴随着与Ago2结合的靶RNA加速去甲腺苷酸化。