DOI: 10.1083/jcb.202201096 ISSN:

T cell proliferation requires ribosomal maturation in nucleolar condensates dependent on DCAF13

Lina Zhou, Shuai Wang, Wei Hu, Xiaoqian Liu, Lingdong Xu, Bolu Tong, Tongtong Zhang, Zhonghui Xue, Yixin Guo, Jing Zhao, Linrong Lu, Hengyu Fan, Wenbin Qian, Jian Chen, Wei Chen, Lie Wang
  • Cell Biology

T cells require rapid proliferation to initiate adaptive immunity to prevent pathogen attacks. The nucleolus, a distinct subnuclear membrane-less compartment for ribosomal biogenesis, is indispensable for cell proliferation. However, specific nucleolar proteins involved in rapid T cell proliferation and their underlying molecular regulatory mechanism remain elusive. Here, we identified an essential nucleolar protein, DCAF13, in T cells and revealed its significant regulation of rapid T cell proliferation. Its depletion drastically impairs T cell proliferation due to severe 18S rRNA maturation failure, consequent abnormal ribosome assembly in nucleoli, and insufficient production of nascent proteins. Mechanistically, we propose that DCAF13 promotes NPM1 phase separation to accelerate pre-RNA enrichment and its endonuclease UTP23 for 18S rRNA maturation during T cell proliferation. Our findings reveal the modulatory effect of nucleolar NPM1/DCAF13 phase separation on ribosomal maturation to ensure rapid T cell proliferation and further pathogen clearance for the first time.

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