美国耶鲁大学医学院Richard A. Flavell研究组取得一项新突破。他们发现BTG1和BTG2（BTG1/2）引起的mRNA不稳定维持T细胞静止。论文发表在2020年3月13日出版的《科学》上。

他们鉴定BTG1和BTG2（BTG1/2）作为负责T细胞静止的因子。BTG1/2缺陷的T细胞由于信使RNA（mRNA）丰度的整体增加而显示出增强的增殖和自发激活，从而降低了激活阈值。

BTG1/2缺乏症会导致聚腺苷酸尾长度增加，从而导致更长的mRNA半衰期。因此，BTG1/2促进了去腺苷酸化和mRNA的降解，以确保T细胞静止。

他们的研究揭示了T细胞静止的关键机制，并表明低mRNA丰度是维持静止的主要特征。

研究人员表示，T细胞在激活前保持静止状态。由于不适当的T细胞活化可能导致疾病，因此必须保持T细胞静止状态。这尽管很重要，但“静态”的基础机制仍未知。

附：英文原文

Title: mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence

Author: Soo Seok Hwang, Jaechul Lim, Zhibin Yu, Philip Kong, Esen Sefik, Hao Xu, Christian C. D. Harman, Lark Kyun Kim, Gap Ryol Lee, Hua-Bing Li, Richard A. Flavell

Issue&Volume: 2020/03/13

Abstract: AbstractT 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.

DOI: 10.1126/science.aax0194

Source: https://science.sciencemag.org/content/367/6483/1255