title: Characterization of Amphioxus IFN Regulatory Factor Family Reveals an Archaic Signaling Framework for Innate Immune Response.
abstract: The IFN regulatory factor (IRF) family encodes transcription factors that play important roles in immune defense, stress response, reproduction, development, and carcinogenesis. Although the origin of the IRF family has been dated back to multicellular organisms, invertebrate IRFs differ from vertebrate IRFs in genomic structure and gene synteny, and little is known about their functions. Through comparison of multiple amphioxus genomes, in this study we suggested that amphioxus contains nine IRF members, whose orthologs are supposed to be shared among three amphioxus species. As the orthologs to the vertebrate IRF1 and IRF4 subgroups, Branchiostoma belcheri tsingtauense (bbt)IRF1 and bbtIRF8 bind the IFN-stimulated response element (ISRE) and were upregulated when amphioxus intestinal cells were stimulated with poly(I:C). As amphioxus-specific IRFs, both bbtIRF3 and bbtIRF7 bind ISRE. When activated, they can be phosphorylated by bbtTBK1 and then translocate into nucleus for target gene transcription. As transcriptional repressors, bbtIRF2 and bbtIRF4 can inhibit the transcriptional activities of bbtIRF1, 3, 7, and 8 by competing for the binding of ISRE. Interestingly, amphioxus IRF2, IRF8, and Rel were identified as target genes of bbtIRF1, bbtIRF7, and bbtIRF3, respectively, suggesting a dynamic feedback regulation among amphioxus IRF and NF-κB. Collectively, to our knowledge we present for the first time an archaic IRF signaling framework in a basal chordate, shedding new insights into the origin and evolution of vertebrate IFN-based antiviral networks.
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Shaochun
authors.identifier: http://orcid.org/0000-0002-8755-7543
authors.initials: S
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Peiyi
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Rirong
authors.initials: R
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China; and Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China lssxal@mail.sysu.edu.cn.
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D006801:Humans; D007113:Immunity, Innate; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D064175:Lancelets; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors