1. Roquin-2 Shares Functions with Its Paralog Roquin-1 in the Repression of mRNAs Controlling T Follicular Helper Cells and Systemic Inflammation.
- Author
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Pratama, Alvin, Ramiscal, Roybel?R., Silva, Diego?G., Das, Souvik?K., Athanasopoulos, Vicki, Fitch, Jessica, Botelho, Natalia?K., Chang, Pheh-Ping, Hu, Xin, Hogan, Jennifer?J., Maña, Paula, Bernal, David, Korner, Heinrich, Yu, Di, Goodnow, Christopher?C., Cook, Matthew?C., and Vinuesa, Carola?G.
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MESSENGER RNA , *T helper cells , *BIOACCUMULATION , *CYTOKINES , *INFLAMMATION , *INTERFERONS , *RNA-protein interactions - Abstract
Summary: 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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