Open AccessPosttranscriptional Control of Type I Interferon Genes by KSRP in the Innate Immune Response against Viral Infection
Author(s) -
Wei Jye Lin,
Xiaojia Zheng,
Chen Yong Lin,
Jun Tsao,
Xiaolin Zhu,
James J. Cody,
Jennifer Coleman,
Roberto Gherzi,
Ming Luo,
Tim M. Townes,
J.B. Parker,
Ching-Yi Chen
Publication year - 2011
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.05073-11
Subject(s) - biology , innate immune system , interferon , interferon type i , messenger rna , vesicular stomatitis virus , rna binding protein , virology , rna splicing , rna , untranslated region , gene expression , immune system , regulation of gene expression , microbiology and biotechnology , virus , gene , immunology , genetics
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 ofIfna andIfnb mRNAs in response to viral infection as a result of decreased mRNA decay. Functional analysis showed that KSRP is required for the decay ofIfna4 andIfnb mRNAs by interaction with AREs. The increased IFN expression rendersKsrp − / − 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.