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Published on: March 5, 2022
N6-methyladenosine regulates PEDV replication and host gene expression
Jianing Chen1, Li Jin1, Zemei Wang1
1State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, 730046, China.
Abstract:
Methylation of the N6 position of adenosine (m6A) is a widespread RNA modification that is critical for various physiological and pathological processes. Although this modification was also found in the RNA of several viruses almost 40 years ago, its biological functions during viral infection have been elucidated recently. Here, we investigated the effects of viral and host RNA methylation during porcine epidemic diarrhea virus (PEDV) infection. The results demonstrated that the m6A modification was abundant in the PEDV genome and the host methyltransferases METTL3 and METTL14 and demethylase FTO were involved in the regulation of viral replication. The knockdown of the methyltransferases increased PEDV replication while silencing the demethylase decreased PEDV output. Moreover, the proteins of the YTHDF family regulated the PEDV replication by affecting the stability of m6A-modified viral RNA. In particular, PEDV infection could trigger an increasement of m6A in host RNA and decrease the expression of FTO. The m6A modification sites in mRNAs and target genes were also altered during PEDV infection. Additionally, part of the host responses to PEDV infection was controlled by m6A modification, which could be reversed by the expression of FTO. Taken together, our results identified the role of m6A modification in PEDV replication and interactions with the host.
Insights
RNA methylation, specifically N6-methyladenosine (m6A), plays a key role in porcine epidemic diarrhea virus (PEDV) infection. This study reveals m6A regulates viral replication and host responses.
Area of Science:
- Virology
- Epigenetics
- Molecular Biology
Background:
- N6-methyladenosine (m6A) is a crucial RNA modification impacting cellular processes.
- The role of m6A in viral infections is an emerging area of research.
- Porcine epidemic diarrhea virus (PEDV) is a significant pathogen in swine.
Purpose of the Study:
- To investigate the impact of m6A RNA modification on PEDV replication.
- To elucidate the roles of host methyltransferases and demethylases in PEDV infection.
- To understand how m6A affects host responses during PEDV infection.
Main Methods:
- Investigated m6A abundance in PEDV RNA and host cells.
- Utilized knockdown of methyltransferases (METTL3, METTL14) and demethylase (FTO).
- Analyzed the effect of YTHDF proteins on m6A-modified viral RNA stability.
- Assessed changes in host RNA m6A sites and gene expression.
Main Results:
- m6A modification is abundant in the PEDV genome.
- METTL3/METTL14 knockdown enhanced PEDV replication; FTO silencing decreased viral output.
- YTHDF proteins modulated PEDV replication via viral RNA stability.
- PEDV infection increased host RNA m6A and decreased FTO expression.
- Host responses to PEDV were influenced by m6A, reversible by FTO.
Conclusions:
- m6A modification is integral to PEDV replication.
- Host m6A machinery (METTL3, METTL14, FTO, YTHDF proteins) significantly influences PEDV.
- PEDV manipulates host m6A levels to affect viral replication and host immunity.
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