4.8 Article

mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence

期刊

SCIENCE
卷 367, 期 6483, 页码 1255-+

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aax0194

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资金

  1. Howard Hughes Medical Institute
  2. Leslie H. Warner Fellowship from Yale Cancer Center (YCC)
  3. HFSPO [LT000037/2018-L]
  4. Jane Coffin Childs Memorial Fund
  5. National Research Foundation of Korea [NRF-2017R1A2B3008621]
  6. National Natural Science Foundation of China [91753141]
  7. Shanghai Jiao Tong University School of Medicine

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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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