Publication in detail

Immunity 2013 Apr 18;38(4):669-80. doi: 10.1016/j.immuni.2013.01.011.

Roquin-2 Shares Functions with Its Paralog Roquin-1 in the Repression of mRNAs Controlling T Follicular Helper Cells and Systemic Inflammation.

Pratama, A; Ramiscal, RR; Silva, DG; Das, SK; Athanasopoulos, V; Fitch, J; Botelho, NK; Chang, PP; Hu, X; Hogan, JJ; Maña, P; Bernal, D; Korner, H; Yu, D; Goodnow, CC; Cook, MC; Vinuesa, CG

John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia.

Abstract:
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-γ (IFN-γ) 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.

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