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

Quiescent naive T cells patrol the body in a resting state, conserving energy and exhibiting slow transcription activity. However, when stimulated, they quickly increase nucleolar protein DCAF13 levels, facilitating nucleolar phase separation mediated by NPM1. This enhances ribosomal RNA maturation and boosts translational activity, supporting cell growth and proliferation. 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.

Automated summary

Quiescent naive T cells conserve energy and exhibit slow transcription activity, but can quickly increase nucleolar protein DCAF13 levels when stimulated, enhancing ribosomal RNA maturation and boosting translational activity for cell growth and proliferation. The specific nucleolar proteins and their regulatory mechanism involved in rapid T cell proliferation remain elusive.