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Roquin-2 Shares Functions with Its Paralog Roquin-1 in the Repression of mRNAs Controlling T Follicular Helper Cells and Systemic Inflammation
journal contributionposted on 2023-05-17, 17:28 authored by Pratama, A, Ramiscal, RR, Silva, DG, Das, SK, Athanasopoulos, V, Fitch, J, Botelho, NK, Chang, PP, Hu, X, Hogan, JJ, Mana, P, Bernal, D, Heinrich KornerHeinrich Korner, Yu, D, Goodnow, CC, Cook, MC, Vinuesa, CG
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-Î³ (IFN-Î³) in TÂ 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. Â© 2013 Elsevier Inc. All rights reserved.
Department/SchoolMenzies Institute for Medical Research
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