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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.
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Soo Seok Hwang
Jaechul Lim
Zhibin Yu
Science
Howard Hughes Medical Institute
Yale University
Shanghai Jiao Tong University
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Hwang et al. (Thu,) studied this question.
www.synapsesocial.com/papers/6a005fd8da5c1eb07f2da4da — DOI: https://doi.org/10.1126/science.aax0194