2. Academic Validation
  3. N-acetyltransferase 10 regulates alphavirus replication via N4-acetylcytidine (ac4C) modification of the lymphocyte antigen six family member E (LY6E) mRNA

N-acetyltransferase 10 regulates alphavirus replication via N4-acetylcytidine (ac4C) modification of the lymphocyte antigen six family member E (LY6E) mRNA

  • J Virol. 2024 Jan 3:e0135023. doi: 10.1128/jvi.01350-23.
Yamei Dang # 1,  Jia Li # 2,  Yuchang Li # 3,  Yuan Wang 1,  Yajing Zhao 4,  Ningbo Zhao 5,  Wanying Li 1 6,  Hui Zhang 1,  Chuantao Ye 7,  Hongwei Ma 1,  Liang Zhang 1,  He Liu 1,  Yangchao Dong 1,  Min Yao 1,  Yingfeng Lei 1,  Zhikai Xu 1,  Fanglin Zhang 1,  Wei Ye 1
Affiliations

Affiliations

  • 1 Department of Microbiology, Airforce Medical University (Fourth Military Medical University), Xi'an, Shaanxi, China.
  • 2 Department of Neurology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, China.
  • 3 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China.
  • 4 Department of Oral and Maxillofacial Surgery, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Airforce Medical University (Fourth Military Medical University), Xi'an, Shaanxi, China.
  • 5 Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
  • 6 Department of Pathogenic Biology, School of Preclinical Medicine, Yan'an University, Yan'an, Shaanxi, China.
  • 7 Department of Infectious Diseases, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi'an, Shaanxi, China.
  • # Contributed equally.
PMID: 38169284 DOI: 10.1128/jvi.01350-23
Abstract

The role of N4-acetylcytidine (ac4C) modification in host mRNA and virus replication is not yet fully understood. In this study, the role of ac4C in the regulation of Sindbis virus (SINV), a prototype alphavirus Infection, was investigated. SINV Infection results in increased levels of N-acetyltransferase 10 (NAT10) and increases the ac4C modification level of cellular RNA. The NAT10 was found to positively regulate SINV Infection in an N-acetyltransferase activity-dependent manner. Mechanistically, the NAT10 modifies lymphocyte antigen six family member E (LY6E) mRNA-the ac4C modification site within the 3'-untranslated region (UTR) of LY6E mRNA, which is essential for its translation and stability. The findings of this study demonstrate that NAT10 regulated mRNA stability and translation efficiency not only through the 5'-UTR or coding sequence but also via the 3'-UTR region. The ac4C modification of host mRNA stability instead of viral mRNA impacting the viral life cycle was thus identified, indicating that the inhibition of ac4C could be a potential target when developing alphavirus antivirals.

Keywords

N-acetyltransferase 10 (NAT10); N4-acetylcytidine (ac4C); Sindbis virus (SINV); alphavirus; lymphocyte antigen 6 family member E (LY6E).

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