2. Academic Validation
  3. Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation

Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation

  • Nat Chem Biol. 2020 Feb;16(2):160-169. 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 5,  Chengqi Yi 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
  • 2 Ludwig Institute for Cancer Research, La Jolla, CA, USA.
  • 3 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 4 Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.
  • 5 Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China. limo@hsc.pku.edu.cn.
  • 6 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. chengqi.yi@pku.edu.cn.
  • 7 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. chengqi.yi@pku.edu.cn.
  • 8 Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, China. chengqi.yi@pku.edu.cn.
  • # Contributed equally.
PMID: 31819270 DOI: 10.1038/s41589-019-0420-5
Abstract

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.

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