ac4C regulates the important functions of EV71 replication

Recently, the research team of Guan Wuxiang, Wuhan Institute of Virology, Chinese Academy of Sciences published a research paper entitled "N4-acetylcytidine regulates the replication and pathogenicity of enterovirus 71" in the international academic journal Nucleic Acids Research.
The function of N4-acetylcytidine (ac4C) modification in the cytoplasmic RNA viral genome was reported, and a new mechanism by which ac4C regulates viral RNA translation and stability by regulating the function of internal ribosome entry sites (IRES) is revealed, which is of great significance
for studying the interaction between virus and host at the epigenetic level.

Chemical modification plays an important role in RNA metabolism and function, and is a hot spot
in the field of epigenetic research.
Methylation modifications (such as m6A, m5C, and Nm) have been shown to play an important role in viral infection, but little is known about ac4C
, the only known acetylation modification in eukaryotic mRNA.
Through mass spectrometry, scientists have found ac4C modifications in the genomes of several RNA viruses such as ZIKV, DENV, HCV, PV and HIV-1, but the molecular mechanism by which ac4C regulates viral replication is unclear
.

In response to this important scientific question, the team conducted an in-depth exploration
of the classical RNA virus EV71.
The study found that EV71 promoted the formation of ac4C modifications in the IRES region of its own 5' untranslated region by changing the cell localization and expression level of the host acetyltransferase NAT10, and these ac4C modifications promoted more efficient replication
of the virus.
Further studies have found that ac4C enhances viral RNA translation by promoting the binding of IRES and PCBP2 and thus improves RNA stability
.
In addition, ac4C can also enhance the binding ability of viral RNA to 3D proteins and the pathogenicity
of viruses in mice.
This study not only reveals the molecular mechanism of ac4C regulating viral infection, but also provides new ideas and possible drug targets for the prevention and treatment of RNA viruses
.

Guan Wuxiang, researcher of Wuhan Institute of Virology, Professor Hu Zhangli of Shenzhen University, and Professor Yuan Jianhui of Shenzhen Nanshan District Center for Disease Control and Prevention are the co-corresponding authors of the paper, and Hao Haojie, a postdoctoral fellow of Wuhan Institute of Virology, is the first author
of the paper.
The research was supported
by the National Natural Science Foundation of China (31970168 and 32000114), the China Postdoctoral Science Foundation (2020M672778), the Hubei Key R&D Program (2021BCD004), and the Hubei Science and Technology Major Project (2021ACB004).

Links to papers: https://doi.
org/10.
1093/nar/gkac675

Figure 1.
Mutations at the ac4C site inhibit viral replication