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.

中文翻译：

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BTG1 和 BTG2 使 mRNA 不稳定维持 T 细胞静止

去腺苷酸或激活？当细胞处于静止状态时，它们会经历可逆的细胞周期停滞并表现出低基础代谢。幼稚 T 细胞通常处于静止状态，直到它们通过 T 细胞受体-共刺激分子信号识别同源抗原。T 细胞静止似乎是一个活跃的过程，但对机制细节知之甚少。黄等人。报道转录因子 BTG1 和 BTG2 在静止 T 细胞中选择性表达。在小鼠中，两种因子有条件地敲除的 T 细胞在体外和对单核细胞增生李斯特菌感染的反应中均显示出增强的增殖和降低的激活阈值。BTG1 和 BTG2 的缺乏导致全球信使 RNA 半衰期增加，这表明信使 RNA 去腺苷酸化和降解是维持 T 细胞静止的重要过程。科学，这个问题 p。1255 个幼稚免疫 T 细胞通过去腺苷酸化主动降低其一般 mRNA 水平来维持其静止状态。T 细胞在激活前保持静止状态。由于不适当的 T 细胞激活会导致疾病，因此必须保持 T 细胞静止。尽管它很重要，但“静止状态”背后的机制仍然难以捉摸。在这里，我们将 BTG1 和 BTG2 (BTG1/2) 确定为负责 T 细胞静止的因素。由于信使 RNA (mRNA) 丰度的整体增加，BTG1/2 缺陷型 T 细胞的增殖和自发激活增加，从而降低了激活阈值。BTG1/2 缺乏导致聚腺苷酸尾长增加，导致更长的 mRNA 半衰期。因此，BTG1/2 促进 mRNA 的去腺苷酸化和降解以确保 T 细胞静止。我们的研究揭示了 T 细胞静止的关键机制，并表明低 mRNA 丰度是维持静止的关键特征。