The KH-type splicing regulatory protein (KSRP) regulates type III interferon expression post-transcriptionally
| Autor: | Rudolf Käfer, Lisa Schmidtke, Katharina Schrick, Hartmut Kleinert, Andrea Pautz, Fabian Gather, Sabrina Saurin, Julia Weinmann-Menke |
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| Rok vydání: | 2018 |
| Předmět: |
Untranslated region
Immunoprecipitation RNA Splicing Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Interferon Cell Line Tumor medicine Animals Humans Heterogeneous Nuclear Ribonucleoprotein D0 Heterogeneous-Nuclear Ribonucleoprotein D Molecular Biology 3' Untranslated Regions 030304 developmental biology Regulation of gene expression Mice Knockout 0303 health sciences Messenger RNA Binding Sites Chemistry RNA-Binding Proteins Cell Biology Dendritic cell Cell biology 030220 oncology & carcinogenesis RNA splicing Trans-Activators Interferons Function (biology) medicine.drug |
| Zdroj: | The Biochemical journal. 476(2) |
| ISSN: | 1470-8728 |
| Popis: | Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell functions. Therefore, it is important to identify cellular mechanisms involved in the control of type III IFN expression. All IFN family members contain AU-rich elements (AREs) in the 3′-untranslated regions (3′-UTR) of their mRNAs that determine mRNA half-life and consequently the expressional level of these cytokines. mRNA stability is controlled by different proteins binding to these AREs leading to either stabilization or destabilization of the respective target mRNA. The KH-type splicing regulatory protein KSRP (also named KHSRP) is an important negative regulator of ARE-containing mRNAs. Here, we identify the interferon lambda 3 (IFNL3) mRNA as a new KSRP target by pull-down and immunoprecipitation experiments, as well as luciferase reporter gene assays. We characterize the KSRP-binding site in the IFNL3 3′-UTR and demonstrate that KSRP regulates the mRNA half-life of the IFNL3 transcript. In addition, we detect enhanced expression of IFNL3 mRNA in KSRP−/− mice, establishing a negative regulatory function of KSRP in type III IFN expression also in vivo. Besides KSRP the RNA-binding protein AUF1 (AU-rich element RNA-binding protein 1) also seems to be involved in the regulation of type III IFN mRNA expression. |
| Databáze: | OpenAIRE |
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