title: Posttranscriptional control of type I interferon genes by KSRP in the innate immune response against viral infection.
abstract: Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3' untranslated regions. Expression of ARE-containing type I interferon transcripts is robustly induced upon viral infection and rapidly shut off thereafter. Their transient accumulation is partly mediated through posttranscriptional regulation. Here we show that mouse embryonic fibroblasts derived from knockout mice deficient in KH-type splicing regulatory protein (KSRP), an RNA-binding protein required for ARE-mediated mRNA decay, produce higher levels of Ifna and Ifnb mRNAs in response to viral infection as a result of decreased mRNA decay. Functional analysis showed that KSRP is required for the decay of Ifna4 and Ifnb mRNAs by interaction with AREs. The increased IFN expression renders Ksrp(-)(/)(-) cells refractory to herpes simplex virus type 1 and vesicular stomatitis virus infection. These findings support a role of a posttranscriptional mechanism in the control of type I IFN expression and highlight the function of KSRP in innate immunity by negatively regulating IFN production.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Wei-Jye
authors.initials: WJ
authors.lastname: Lin
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Zheng
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Tsao
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhu
authors.forename: James J
authors.initials: JJ
authors.lastname: Cody
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Coleman
authors.forename: Roberto
authors.initials: R
authors.lastname: Gherzi
authors.forename: Ming
authors.initials: M
authors.lastname: Luo
authors.forename: Tim M
authors.initials: TM
authors.lastname: Townes
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Parker
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006561:Herpes Simplex / Q000276:immunology; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics*; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D034622:RNA Interference / Q000276:immunology*; D020871:RNA Stability / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; C507913:Khsrp protein, mouse; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D016899:Interferon-beta