mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence

Science. 2020 Mar 13;367(6483):1255-1260. doi: 10.1126/science.aax0194.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / physiology*
  • Lymphocyte Activation*
  • Mice
  • Mice, Knockout
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Polyadenylation
  • RNA Stability*
  • RNA, Messenger / chemistry*
  • T-Lymphocytes / immunology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • Btg1 protein, mouse
  • Btg2 protein, mouse
  • Immediate-Early Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins