LAUSR

Deadenylate or activate? When cells are quiescent, they undergo reversible cell cycle arrest and evince low basal metabolism. Naïve T cells are normally quiescent until they recognize cognate antigens through T cell receptor–costimulatory molecule signaling. T cell quiescence appears to be an active process, but the mechanistic details are poorly understood. Hwang et al. report that the transcription factors BTG1 and BTG2 are selectively expressed in quiescent T cells. In mice, T cells conditionally knocked out for both factors showed enhanced proliferation and a lowered threshold of activation both in vitro and in response to Listeria monocytogenes infection. Deficiency of BTG1 and BTG2 resulted in increases in global messenger RNA half-life, suggesting that messenger RNA deadenylation and degradation are important processes for maintaining T cell quiescence. Science, this issue p. 1255 Naïve immunological T cells maintain their quiescent state by actively minimizing their general mRNA levels via deadenylation. T cells maintain a quiescent state prior to activation. As inappropriate T cell activation can cause disease, T cell quiescence must be preserved. Despite its importance, the mechanisms underlying the “quiescent state” remain elusive. Here, we identify BTG1 and BTG2 (BTG1/2) as factors responsible for T cell quiescence. BTG1/2-deficient T cells show an increased proliferation and spontaneous activation due to a global increase in messenger RNA (mRNA) abundance, which reduces the threshold to activation. BTG1/2 deficiency leads to an increase in polyadenylate tail length, resulting in a greater mRNA half-life. Thus, BTG1/2 promote the deadenylation and degradation of mRNA to secure T cell quiescence. Our study reveals a key mechanism underlying T cell quiescence and suggests that low mRNA abundance is a crucial feature for maintaining quiescence.