Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation.,Nature Chemical Biology

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Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation.
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2019-12-09 , DOI: 10.1038/s41589-019-0420-5
Jinghui Song ₁ , Yuan Zhuang ₁ , Chenxu Zhu _{1,

2} , Haowei Meng ₁ , Bo Lu _{1,

3} , Bingteng Xie ₄ , Jinying Peng ₁ , Mo Li ₄ , Chengqi Yi _{1,

3,

5}

Affiliation

Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 results in a marked reduction of the expression level of a large number of mature miRNAs and concomitant accumulation of unprocessed primary microRNAs (pri-miRNAs) in multiple human cells. Mechanistically, PUS10 directly binds to pri-miRNAs and interacts with the microprocessor to promote miRNA biogenesis. Unexpectedly, this process is independent of the catalytic activity of PUS10. Additionally, we develop a sequencing method to profile Ψ in the tRNAome and report PUS10-dependent Ψ sites in tRNA. Collectively, our findings reveal differential functions of PUS10 in nuclear miRNA processing and in cytoplasmic tRNA pseudouridylation.

中文翻译：

人类PUS10在miRNA加工和tRNA假尿苷化中的不同作用。

假尿苷合酶（PUSs）负责在RNA中安装假尿苷（β）修饰。但是，PUS酶的活性和功能在很大程度上尚待探索。在这里，我们重点研究人PUS10，并发现它与微处理器（DROSHA-DGCR8复合体）共表达。PUS10的耗尽会导致大量成熟miRNA的表达水平显着降低，以及未加工的一级microRNA（pri-miRNA）在多个人类细胞中的积累。从机理上讲，PUS10直接与pri-miRNA结合并与微处理器相互作用以促进miRNA的生物发生。出乎意料的是，该过程与PUS10的催化活性无关。此外，我们开发了一种测序方法来分析tRNAome中的and，并报告tRNA中依赖PUS10的Ψ位点。总的来说，

更新日期：2019-12-11

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