T cell proliferation requires ribosomal maturation in nucleolar condensates dependent on DCAF13
T cell proliferation requires ribosomal maturation in nucleolar condensates dependent on DCAF13
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DOI：
10.1083/jcb.202201096
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发表时间：
2023-08
期刊：
影响因子：
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通讯作者：
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
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文献类型：
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作者：
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
T细胞需要快速增殖以启动适应性免疫，以防止病原体攻击。核仁是核糖体生物发生的一个独特的亚核内无膜区，对细胞增殖是不可或缺的。然而，参与T细胞快速增殖的特定核仁蛋白及其潜在的分子调控机制仍然不清楚。在这里，我们在T细胞中发现了一种重要的核仁蛋白DCAF13，并揭示了它对T细胞快速增殖的重要调节作用。由于严重的18S rRNA成熟失败，导致核仁中核糖体组装异常，以及新生蛋白的产生不足，它的缺失严重损害了T细胞的增殖。从机制上讲，我们认为DCAF13促进NPM1的时相分离，以促进T细胞增殖过程中前RNA的浓缩及其内切酶UTP23对18S rRNA的成熟。我们的发现首次揭示了核仁NPM1/DCAF13相分离对核糖体成熟的调制作用，以确保T细胞的快速增殖和进一步的病原体清除。
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.