METTL14 and FTO mediated m6A modification regulate PCV2 replication by affecting miR-30a-5p maturity

Chen Li; Xiaoyan Wu; Ying Yang; Jianli Shi; Shuo Wang; Jiaxin Li; Yao Tian; Chang Liu; Hong Han; Shaojian Xu; Xianjie Han; Yingru Ma; Limei Zheng; Jun Li

doi:10.1080/21505594.2023.2232910

METTL14 and FTO mediated m⁶A modification regulate PCV2 replication by affecting miR-30a-5p maturity

Virulence. 2023 Dec;14(1):2232910. doi: 10.1080/21505594.2023.2232910.

Authors

Chen Li¹, Xiaoyan Wu^{1

2}, Ying Yang², Jianli Shi¹, Shuo Wang³, Jiaxin Li⁴, Yao Tian⁴, Chang Liu¹, Hong Han¹, Shaojian Xu¹, Xianjie Han⁴, Yingru Ma⁴, Limei Zheng⁴, Jun Li^{1

2

4}

Affiliations

¹ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, jinan, P. R. China.
² College of Life Sciences, Shandong Normal University, Jinan, China.
³ Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, China.
⁴ College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China.

Abstract

The epigenetic modification of the N6-methyladenosine (m⁶A) methylation plays an important role in virus infection and replication. However, its role in Porcine circovirus type 2 (PCV2) replication has not been well studied. Here, we demonstrated that m⁶A modifications are increased in PK-15 cells after PCV2 infection. In particular, PCV2 infection could increase the expression of methyltransferase METTL14 and demethylase FTO. Moreover, interfering with METTL14 accumulation reduced the m⁶A methylation level and virus reproduction, whereas depleting the FTO demethylase enhanced the m⁶A methylation level and stimulated virus reproduction. Besides, we showed that METTL14 and FTO regulate PCV2 replication by affecting the process of miRNA maturity, especially the miRNA-30a-5p. Taken together, our results demonstrated that the m⁶A modification positively affects PCV2 replication and the role of m⁶A modification in the replication mechanism of the PCV2 virus provides a new idea for the prevention and control of the PCV2.

Keywords: Porcine circovirus type 2; m6A modification; miRNA maturity; replication.

MeSH terms

Animals
Cell Line
Circovirus* / genetics
Methyltransferases / genetics
MicroRNAs* / genetics
Swine
Virus Replication / physiology

Substances

MicroRNAs
Methyltransferases

Grants and funding

This work was supported by grants from the Major Scientific and Technological Innovation Project (MSTIP) (grant no. 2019JZZY010720), the Shandong Province Pig Industry Technology System (grant no. SDAIT-08-06), the Shandong Province agricultural applications of major innovation projects (grant no. SD2019XM003, SD2019XM006), the Agricultural Science and Technology Innovation Project of Shandong Academy of Agricultural Sciences (grant no. CXGC2018E10, CXGC2023G03, CXGC2023E02 and CXGC2023A21), and The Natural Fund of Shandong Province (grant no. ZR2022MC011).