Noncoding Y RNAs regulate the levels, subcellular distribution and protein interactions of their Ro60 autoantigen partner.
Noncoding Y RNAs regulate the levels, subcellular distribution and protein interactions of their Ro60 autoantigen partner.
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非编码 Y RNA 调节 Ro60 自身抗原伴侣的水平、亚细胞分布和蛋白质相互作用。
DOI：
10.1093/nar/gkaa414
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发表时间：
2020
影响因子：
14.9
通讯作者：
Wolin,SandraL
中科院分区：
文献类型：
--
作者：
Leng,Yuanyuan;Sim,Soyeong;Magidson,Valentin;Wolin,SandraL
非编码Y RNA在动物细胞中丰富，并存在于许多细菌中。这些RNA被Ro60结合并稳定，Ro60是一种环状蛋白，是系统性红斑狼疮患者自身抗体的靶点。在细菌中的研究表明，Y RNA将Ro60拴在一个环形的核糖核酸外切酶上，形成了一个专门用于结构化RNA降解的双环RNP机器。除了充当系链之外，细菌RNA还控制底物进入Ro60腔。为了确定Y RNA在哺乳动物中的作用，我们使用CRISPR来产生缺乏两种鼠Y RNA中的一种或两种的小鼠胚胎干细胞。尽管有报道称动物细胞Y RNA对DNA复制至关重要，但缺乏这些RNA的细胞正常分裂。然而，Ro60水平降低，表明Ro60积累到野生型水平需要Y RNA结合。Y RNA调节Ro60的亚细胞位置，因为当Y RNA不存在时，Ro60在细胞质中减少，在核仁中增加。最后，我们表明Y RNA将Ro60拴在不同的效应蛋白上以产生专门的RNP。总之，我们的数据表明Y RNA的作用与其Ro60伴侣的作用密切相关。
Noncoding Y RNAs are abundant in animal cells and present in many bacteria. These RNAs are bound and stabilized by Ro60, a ring-shaped protein that is a target of autoantibodies in patients with systemic lupus erythematosus. Studies in bacteria revealed that Y RNA tethers Ro60 to a ring-shaped exoribonuclease, forming a double-ringed RNP machine specialized for structured RNA degradation. In addition to functioning as a tether, the bacterial RNA gates access of substrates to the Ro60 cavity. To identify roles for Y RNAs in mammals, we used CRISPR to generate mouse embryonic stem cells lacking one or both of the two murine Y RNAs. Despite reports that animal cell Y RNAs are essential for DNA replication, cells lacking these RNAs divide normally. However, Ro60 levels are reduced, revealing that Y RNA binding is required for Ro60 to accumulate to wild-type levels. Y RNAs regulate the subcellular location of Ro60, since Ro60 is reduced in the cytoplasm and increased in nucleoli when Y RNAs are absent. Last, we show that Y RNAs tether Ro60 to diverse effector proteins to generate specialized RNPs. Together, our data demonstrate that the roles of Y RNAs are intimately connected to that of their Ro60 partner.