RNA-binding protein HuR interacts with thrombomodulin 5'untranslated region and represses internal ribosome entry site-mediated translation under IL-1 beta treatment
| Autor: | Chin Hsu, Chiu Hung Yeh, Pin Tse Lee, Wen Chang Chang, Liang Yi Hung, Yi Tseng Lin, Joseph T. Tseng, Shu Yun Le, Wan Lin Liao |
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| Rok vydání: | 2008 |
| Předmět: |
Untranslated region
Five prime untranslated region Thrombomodulin Interleukin-1beta ELAV-Like Protein 1 RNA-binding protein Biology Models Biological Cell Line Tumor Sepsis medicine Protein biosynthesis Animals Humans Molecular Biology Messenger RNA RNA-Binding Proteins Cell Biology Articles Molecular biology Internal ribosome entry site Disease Models Animal ELAV Proteins Gene Expression Regulation Protein Biosynthesis Antigens Surface RNA 5' Untranslated Regions Ribosomes Protein C medicine.drug |
| Zdroj: | Molecular biology of the cell. 19(9) |
| ISSN: | 1939-4586 |
| Popis: | Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5′ untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5′UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1β, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5′UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1β treatment and sepsis. |
| Databáze: | OpenAIRE |
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