mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence
Soo Seok Hwang, Jaechul Lim, Zhibin Yu, Philip Kong, Esen Sefik, Hao Xu, Christian C. D. Harman, Lark Kyun Kim, Gap Ryol Lee, Huabing Li, Richard A. Flavell
Abstract
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.