| First Author | Zhao W | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 4 | Pages | 1778-85 |
| PubMed ID | 18042545 | Mgi Jnum | J:130721 |
| Mgi Id | MGI:3772158 | Doi | 10.1074/jbc.M707573200 |
| Citation | Zhao W, et al. (2008) p38alpha stabilizes interleukin-6 mRNA via multiple AU-rich elements. J Biol Chem 283(4):1778-85 |
| abstractText | AU-rich elements (AREs) in the 3'-untranslated region (UTR) of unstable mRNA dictate their degradation or mediate translational repression. Cell signaling through p38alpha MAPK is necessary for post-transcriptional regulation of many pro-inflammatory cytokines. Here, the cis-acting elements of interleukin-6 (IL-6) 3'-UTR mRNA that required p38alpha signaling for mRNA stability and translation were identified. Using mouse embryonic fibroblasts (MEFs) derived from p38alpha(+/+) and p38alpha(-/-) mice, we observed that p38alpha is obligatory for the IL-1-induced IL-6 biosynthesis. IL-6 mRNA stability is promoted by p38alpha via 3'-UTR. To understand the mechanism of cis-elements regulated by p38alpha at post-transcriptional level, truncation of 3'-UTR and the full-length 3'-UTR with individual AUUUA motif mutation placed in gene reporter system was employed. Mutation-based screen performed in p38alpha(+/+) and p38alpha(-/-) mouse embryonic fibroblast cells revealed that ARE1, ARE2, and ARE5 in IL-6 3'-UTR were targeted by p38alpha, and truncation-based screen showed that IL-6 3'-UTR-(56-173) was targeted by p38alpha to stable mRNA. RNA secondary structure analysis indicated that modulated reporter gene expression was consistent with predicted secondary structure changes. |
