Roquin paralogs add a new dimension to ICOS regulation

Abstract

Two studies in the current issue of Immunity (Pratama et al., 2013; Vogel et al., 2013) demonstrate that the RNA-binding proteins Roquin-1 and Roquin-2 have redundant function in the posttranscriptional repression of Icos messenger RNA by CD4(+) T cells.

Figure 1. Roquin-1 and -2 redundantly suppress Icos mRNA expression in CD4⁺ T cells

In wildtype CD4⁺ T cells, Roquin-1 binds target mRNAs in stress granules, promoting their degradation via RNA decay proteins Edc4 and Rck. Rc3h1^san/san (sanroque) mice express a mutant Roquin-1 protein that binds mRNA, yet lacks the capacity to promote its degradation, while preventing the accumulation of Roquin-2 in the stress granules and subsequent compensatory repression of target transcripts, including Icos. Overexpression of ICOS in sanroque mice leads to an accumulation of Tfh cells and robust GC responses, with systemic autoimmunity. In mice lacking Roquin-1, Roquin-2 reduntantly suppresses Icos mRNA, preventing Tfh cell expansion. By contrast, mice lacking Roquin-1 and -2 fail to suppress Icos expression, phenocopying the sanroque strain.