RNA-binding protein HuR coordinately regulates genes essential for Th2 polarization and function at the posttranscriptional level (99.7)
| Autor: | Matthew Gubin, Cristiana Stellato, Vincenzo Casolaro, Danielle Tartar, Joseph Magee, Jing Chen, Robert Calaluce, Ulus Atasoy |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:99.7-99.7 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Posttranscriptional gene regulation controls the expression of genes implicated in a variety of processes, including those of the immune system. The RNA-binding protein HuR regulates many early response genes as well as cytokines such as IL-4 and IL-13. Therefore, HuR has been implicated in regulating Th2 polarization and cytokine production. GATA-3, a transcription factor that is essential for Th2 polarization contains a putative HuR binding site in its 3’UTR. Immunoprecipitation (IP) of ribonucleoprotein complexes with an anti-HuR Ab revealed significant enrichment for GATA-3 mRNA. HuR association with GATA-3 3’UTR was confirmed by biotin pull-downs. To understand the role of HuR in Th2 polarization in vivo we generated a transgenic HuR CD4+ T-cell mouse model. Th2-skewed cells over-expressing HuR displayed increases in both numbers of GATA3-expressing cells, and in overall GATA-3 expression. The frequency of Th2-polarized cells, but not of Th1, increased in CD4+ T cell HuR transgenic cells and the levels of secreted IL-4 and IL-13, but not IFN-γ, also increased significantly in both activated splenocytes and polarized cells. Furthermore, a knockdown of HuR in Jurkat cells decreased protein levels of GATA-3. Hence, HuR may be functioning to coordinately posttranscriptionally regulate genes essential for Th2 polarization and function. Better understanding of posttranscriptional regulation may elucidate control mechanisms of naïve CD4+ Th2 polarization. |
| Databáze: | OpenAIRE |
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