| First Author | Pratama A | Year | 2013 |
| Journal | Immunity | Volume | 38 |
| Issue | 4 | Pages | 669-80 |
| PubMed ID | 23583642 | Mgi Jnum | J:196137 |
| Mgi Id | MGI:5486593 | Doi | 10.1016/j.immuni.2013.01.011 |
| Citation | Pratama A, et al. (2013) Roquin-2 Shares Functions with Its Paralog Roquin-1 in the Repression of mRNAs Controlling T Follicular Helper Cells and Systemic Inflammation. Immunity 38(4):669-80 |
| abstractText | Accumulation of T follicular helper (Tfh) cells and proinflammatory cytokines drive autoantibody-mediated diseases. The RNA-binding protein Roquin-1 (Rc3h1) represses the inducible costimulator ICOS and interferon-gamma (IFN-gamma) in T cells to prevent Tfh cell accumulation. Unlike Rc3h1(san) mice with a mutation in the ROQ domain of Roquin-1, mice lacking the protein, paradoxically do not display increased Tfh cells. Here we have analyzed mice with mutations that eliminate the RING domain from Roquin-1 or its paralog, Roquin-2 (Rc3h2). RING or ROQ mutations both disrupted Icos mRNA regulation by Roquin-1, but, unlike the ROQ mutant that still occupied mRNA-regulating stress granules, RING-deficient Roquin-1 failed to localize to stress granules and allowed Roquin-2 to compensate in the repression of ICOS and Tfh cells. These paralogs also targeted tumor necrosis factor (TNF) in nonlymphoid cells, ameliorating autoantibody-induced arthritis. The Roquin family emerges as a posttranscriptional brake in the adaptive and innate phases of antibody responses. |
