| First Author | Salerno F | Year | 2018 |
| Journal | Nat Immunol | Volume | 19 |
| Issue | 8 | Pages | 828-837 |
| PubMed ID | 29988089 | Mgi Jnum | J:282498 |
| Mgi Id | MGI:6381068 | Doi | 10.1038/s41590-018-0155-6 |
| Citation | Salerno F, et al. (2018) Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells. Nat Immunol 19(8):828-837 |
| abstractText | Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3' untranslated region (3' UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in the Ifng-3' UTR led to chronic cytokine production in memory T cells. This aberrant protein production did not result from increased expression and/or half-life of the mRNA. Instead, AREs blocked the recruitment of cytokine-encoding mRNA to ribosomes; this block depended on the ARE-binding protein ZFP36L2. Thus, AREs mediate repression of translation in mouse and human memory T cells by preventing undesirable protein production from pre-formed cytokine-encoding mRNAs in the absence of infection. |
