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N6-methyladenosine reader protein YTHDC1 regulates influenza A virus NS segment splicing and replication
Yinxing Zhu1,2, Ruifang Wang1,2, Jiahui Zou1,2
1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Plos Pathogens
|April 13, 2023
Summary
The study reveals how the YTHDC1 protein impacts influenza A virus (IAV) mRNA splicing. This finding offers a potential therapeutic target for blocking influenza virus infection and developing new vaccines.
Area of Science:
- Virology
- Molecular Biology
- Epigenetics
Background:
- N6-methyladenosine (m6A) RNA modification influences viral infectivity.
- m6A modifications are common in influenza viral RNAs, but their role in viral mRNA splicing is unclear.
Purpose of the Study:
- To investigate the role of m6A reader proteins in influenza A virus (IAV) mRNA splicing.
- To identify host factors involved in IAV replication and pathogenicity.
Main Methods:
- Identification of YTHDC1 as an m6A reader protein interacting with IAV NS1.
- Analysis of YTHDC1's effect on viral mRNA splicing using molecular biology techniques.
- In vitro and in vivo studies to assess the impact of YTHDC1 on IAV replication and pathogenicity.
Main Results:
- YTHDC1 associates with IAV NS1 protein and modulates viral mRNA splicing.
- IAV infection enhances YTHDC1 levels.
- YTHDC1 inhibits NS splicing by binding to an NS 3' splicing site, promoting IAV replication and pathogenicity.
Conclusions:
- YTHDC1 is a host factor that plays a critical role in regulating IAV mRNA splicing.
- Targeting YTHDC1 could be a therapeutic strategy against influenza virus infections.
- Understanding YTHDC1's function provides insights for developing attenuated influenza vaccines.
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