X-protein Negatively Regulate Type Ⅰ Interferon-mediated Innate Antiviral Responses
作者单位：Peking Union Medical College
会议名称：《第十三届全国免疫学学术大会》
会议日期：2018年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
关 键 词：innate immunity type Ⅰ interferon ISGs X-protein FOXO3
摘 要：The interferon(IFN)-mediated innate antiviral immune response provides a robust first line of defense against invading pathogens, and interferon-stimulated genes(ISGs) are essential effectors of *** regulation of ISGs is one of contributors to the pathogenesis of abortive antiviral responses and autoimmune ***-transcriptomic regulation plays key roles in diverse biological processes, including defining cell status and affecting cell differentiation.N-methyladenosine(mA) modification is the most abundant internal modification in eukaryotic mRNA and has been discovered as the first example of reversible RNA ***, we found that the mA reader X-protein suppresses ISGs constitutive expression by promoting translation of the transcription co-repressor *** cooperation with two cofactors, PABP1 and eIF4G2, X-protein binds to the translation initiation region(TIR) of FOXO3 mRNA and promotes FOXO3 *** the YTH and P/Q/N-rich domains of X-protein are required for its binding capacity to FOXO3 ***, METTL3-mediated mA modification was not involved in this ***, X-gene deficiency mice have increased ISGs levels and enhanced resistance to several virus *** findings identify X-protein as a negative regulator of antiviral immunity through translational promotion of FOXO3 mRNA under homeostatic conditions, adding insight into the network of RBP-RNA interactions in maintaining host antiviral immune function and preventing inflammatory response.