Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation.

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.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Song J,Zhuang Y,Zhu C,Meng H,Lu B,Xie B,Peng J,Li M,Yi C

doi

10.1038/s41589-019-0420-5

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

160-169

issue

2

eissn

1552-4450

issn

1552-4469

pii

10.1038/s41589-019-0420-5

journal_volume

16

pub_type

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