N4-acetylcytidine regulates the replication and pathogenicity of enterovirus 71

Author:

Hao Haojie1234,Liu Weichi4,Miao Yuanjiu45,Ma Li45,Yu Baocheng45,Liu Lishi45,Yang Chunjie4,Zhang Kui45,Chen Zhen4,Yang Jingwen4,Zheng Zhenhua4,Zhang Bo4ORCID,Deng Fei4,Gong Peng4ORCID,Yuan Jianhui6,Hu Zhangli1ORCID,Guan Wuxiang47ORCID

Affiliation:

1. College of Life Sciences and Oceanography, Shenzhen University , Shenzhen 518060, China

2. College of Physics and Optoelectronic Engineering, Shenzhen University , Shenzhen 518060, China

3. Hanshan Normal University , Chaozhou 521041, China

4. Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, Hubei 430071, China

5. University of Chinese Academy of Sciences , Beijing 100049, China

6. Nanshan District Center for Disease Control and Prevention , Shenzhen 518054, China

7. Hubei JiangXia Laboratory , Wuhan, Hubei 430200, China

Abstract

Abstract Chemical modifications are important for RNA function and metabolism. N4-acetylcytidine (ac4C) is critical for the translation and stability of mRNA. Although ac4C is found in RNA viruses, the detailed mechanisms through which ac4C affects viral replication are unclear. Here, we reported that the 5′ untranslated region of the enterovirus 71 (EV71) genome was ac4C modified by the host acetyltransferase NAT10. Inhibition of NAT10 and mutation of the ac4C sites within the internal ribosomal entry site (IRES) suppressed EV71 replication. ac4C enhanced viral RNA translation via selective recruitment of PCBP2 to the IRES and boosted RNA stability. Additionally, ac4C increased the binding of RNA-dependent RNA polymerase (3D) to viral RNA. Notably, ac4C-deficient mutant EV71 showed reduced pathogenicity in vivo. Our findings highlighted the essential role of ac4C in EV71 infection and provided insights into potential antiviral treatments.

Funder

National Natural Science Foundation of China

China Postdoctoral Science Foundation

Key R&D Program of Hubei Province

Hubei Science and Technology

Publisher

Oxford University Press (OUP)

Subject

Genetics

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