CellRes Release Antiviral Protein From Chinese Academy Of Sciences Research Achievements

Article author is Liu Yingfang researcher at the Institute of Chinese Academy of Sciences, whose main research interests include aging and apoptosis-related proteins in structural biology. This study is done with Shu hongbing, Wuhan University, academician of group cooperation. Biophysical Yang Zhenlin, Liang Huanhuan and Wuhan University, Zhou Qian for the joint first authors of the article. The research from the Ministry of science and technology, supported by the National Natural Science Foundation and Chinese Academy of Sciences.

Type I interferon (IFN) by stimulating called interferon-inducible genes (interferon-stimulated genes, ISG) of various antiviral gene expression to prevent viral replication, including 56 of the interferon-induced gene (ISG56) family members. ISG56 family 4: ISG54 (IFIT2), ISG56 (IFIT1), ISG58 (IFIT5) and ISG60 (IFIT3), with overlapping functions between them but inducing patterns vary. Past studies have proven that the virus ISG56 family members in preventing viral replication and plays a very important role in the regulation of cell function, but for the basic molecular mechanism is not well understood.

Graduate into mechanisms for this protein family in recent years a large number of inconsistent results. Earlier studies showed that ISG54 and ISG56 and translation inhibition of translation initiation factor eIF3e and eIF3c interactions. ISG56 family proteins was found later through lack of recognition of 2 '-o-methylation of viral mRNA to suppress the virus. Recent studies have reported that ISG56 is by 5 '-triphosphate RNA binding ability to inhibit viral replication. In addition, the ISG56 family of proteins involved in was also raised, such as IFN signaling, apoptosis and cell migration, cell regulation of cellular processes in the inflammatory process. Although these results provided to the members of the ISG56 family of antiviral mechanisms important to understand and need more detailed structural information to clarify the molecular mechanisms of these features

In this article, researchers resolved the Crystal structure of human ISG54, and found that it has the structure of a novel RNA-binding protein, which contains 9 tetratricopeptide repeat-like domain, forms domain-swapped two-body. ISG54 c-folded into a supercoiled structure, can be used to combine virus mRNA. These RNA-binding sites of key residues after mutation, ISG54 will lose its anti-virus RNA binding ability and functionality. Accidental discoveries in the study, ISG54 for RNA sequences with strong selectivity, which tend to combine AU-rich RNA, which does not depend on the mRNA Cap and characteristics of 5' triphosphate. Further research shows that the ISG54 protein can be combined with cytokine mRNA ARE sequences of non-coding regions, as ARE an important role for regulation of mRNA stability, the researchers speculate that this may be ISG54 play a key cell functions.

As the first of the ISG56 family proteins, which is important for the explanation of function mechanism of ISG56 family members.