Cao Xuetao team proposed a new mechanism for the apparent regulation of antiviral natural immunity

Release date: 2017-08-30

On August 29, "Nature-Immunology" published a paper by the research team of the Chinese Academy of Medical Sciences and the academician of the Chinese Academy of Engineering, Cao Xuetao, and reported that the RNA helicase DDX46 can be demethylated by RNA to cause the antiviral effector mRNA nucleus. Results of studies that arrest and thereby inhibit the antiviral innate immune response.

Interferon plays a key role in the body's antiviral natural immune response. During the viral infection process, the amount and duration of interferon production are precisely regulated to ensure that the body clears the invading virus while avoiding pathological autoimmune damage. At present, the molecular mechanism of precise regulation of interferon expression is mainly focused on the natural immune signaling pathway protein molecule, and the mechanism of regulating interferon expression by means of RNA modification in the nucleus is still unclear.

Academician Cao Xuetao and Zheng Qingliang, postdoctoral fellow of the Institute of Basic Science of the Chinese Academy of Medical Sciences, and Hou Jin, a professor of the State Key Laboratory of Medical Immunology at the Second Military Medical University, jointly tackled the problem of RNA recognition and metabolism and regulation of DEAD-box helicase (DDX) family members. The important function of the virus in the natural immune response, by screening a variety of DDX family members in the role of viral infection macrophages innate immune response, found that DDX46 can significantly inhibit the expression of interferon induced by viral infection.

Studies have shown that DDX46 binds to the CCGGUU conserved motif of antiviral effector mRNA. When viral infection, DDX46 binds to m6A demethylase ALKBH5, which demethylates antiviral effector mRNA that binds to DDX46. Modification leads to its nuclear retention, which blocks the expression of proteins of these antiviral effector molecules, thereby reducing interferon production and ultimately inhibiting the antiviral innate immune response.

This study revealed that RNA helicase DDX46 participates in the regulation of antiviral natural immune responses through a new way of RNA modification in the nucleus, and proposes a new natural immune and inflammatory regulatory mechanism, providing a mechanism for the prevention and treatment of viral infections and inflammatory diseases. New potential targets and ideas.

Source: Chinese Journal of Science

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