LC Domain-Mediated Coalescence Is Essential for Otu Enzymatic Activity to Extend Drosophila Lifespan
LC Domain-Mediated Coalescence Is Essential for Otu Enzymatic Activity to Extend Drosophila Lifespan
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LC 结构域介导的聚结对于 Otu 酶活性延长果蝇寿命至关重要
DOI：
10.1016/j.molcel.2019.02.004
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发表时间：
2019-04-18
期刊：
影响因子：
16
通讯作者：
Chen, Dahua
中科院分区：
文献类型：
--
作者：
Ji, Shanming;Luo, Yuewan;Chen, Dahua
在真核细胞中，RNA结合蛋白（RBP）与RNA相互作用，形成长期认为调节RNA命运或活性的核糖核蛋白复合物（RNA颗粒）。新兴证据表明，一些RBP不仅结合RNA，而且具有与泛素调节有关的酶促活性，从而提出了这些RBP形成的RNA颗粒是否调节泛素信号传导和相关生物学功能的重要问题。在这里，我们表明果蝇通过其本质上无序的低复杂性结构域结合RNA和联合与无膜的生物分子冷凝物结合，而合并代表了驱动去泛素酶活性的OTU的功能态。值得注意的是，OTU的合并赋予的酶促活性受其结合的RNA和伴侣BAM的阳性调节。进一步的遗传分析表明，OTU/BAM去泛素酶复合物和DTRAF6构成了在衰老过程中维持肠道免疫稳态的反馈回路，从而控制了寿命。因此，受调节的生物分子冷凝物可能代表控制动态酶活性和相关生物学过程的机制。
In eukaryotic cells, RNA-binding proteins (RBPs) interact with RNAs to form ribonucleoprotein complexes (RNA granules) that have long been thought to regulate RNA fate or activity. Emerging evidence suggests that some RBPs not only bind RNA but also possess enzymatic activity related to ubiquitin regulation, raising important questions of whether these RBP-formed RNA granules regulate ubiquitin signaling and related biological functions. Here, we show that Drosophila Otu binds RNAs and coalesces to membrane-less biomolecular condensates via its intrinsically disordered low-complexity domain, and coalescence represents a functional state for Otu exerting deubiquitinase activity. Notably, coalescencemediated enzymatic activity of Otu is positively regulated by its bound RNAs and co-partner Bam. Further genetic analysis reveals that the Otu/Bam deubiquitinase complex and dTraf6 constitute a feedback loop to maintain intestinal immune homeostasis during aging, thereby controlling longevity. Thus, regulated biomolecular condensates may represent a mechanism that controls dynamic enzymatic activities and related biological processes.