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Published on: May 1, 2019
METTL14 and FTO mediated m6A modification regulate PCV2 replication by affecting miR-30a-5p maturity
Chen Li1, Xiaoyan Wu1,2, Ying Yang2
1Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, jinan, P. R. 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.
Insights
N6-methyladenosine (m6A) methylation positively impacts Porcine circovirus type 2 (PCV2) replication. Targeting methyltransferase METTL14 and demethylase FTO offers new strategies for PCV2 prevention and control.
Area of Science:
- Epigenetics
- Virology
- Molecular Biology
Background:
- N6-methyladenosine (m6A) methylation is crucial in viral infections.
- The role of m6A in Porcine circovirus type 2 (PCV2) replication remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of m6A modification in PCV2 replication.
- To elucidate the mechanisms by which m6A affects PCV2 virus reproduction.
Main Methods:
- PK-15 cells were infected with PCV2.
- Expression levels of METTL14 and FTO were analyzed.
- m6A methylation levels were assessed following manipulation of METTL14 and FTO.
- miRNA maturity, specifically miRNA-30a-5p, was evaluated.
Main Results:
- PCV2 infection increased m6A levels in PK-15 cells.
- PCV2 infection upregulated the expression of METTL14 and FTO.
- Inhibition of METTL14 reduced m6A levels and PCV2 replication.
- Depletion of FTO increased m6A levels and stimulated PCV2 replication.
- METTL14 and FTO were found to regulate PCV2 replication via miRNA-30a-5p maturation.
Conclusions:
- m6A modification positively regulates PCV2 replication.
- METTL14 and FTO are key players in PCV2 replication through epigenetic mechanisms.
- Understanding the m6A pathway offers novel avenues for PCV2 control.
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