TY - JOUR
T1 - Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation
AU - Song, Jinghui
AU - Zhuang, Yuan
AU - Zhu, Chenxu
AU - Meng, Haowei
AU - Lu, Bo
AU - Xie, Bingteng
AU - Peng, Jinying
AU - Li, Mo
AU - Yi, Chengqi
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076376610&partnerID=8YFLogxK
U2 - 10.1038/s41589-019-0420-5
DO - 10.1038/s41589-019-0420-5
M3 - Article
C2 - 31819270
AN - SCOPUS:85076376610
SN - 1552-4450
VL - 16
SP - 160
EP - 169
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 2
ER -