Dynamic phosphorylation of TCOF1 controlled by CK2 and PPM1D regulates nucleolar condensation and RNA polymerase I activity.

PPM1D dephosphorylates CK2-phosphorylated TCOF1 to regulate nucleolar condensation and RNA polymerase I activity, and disrupting this balance reduces rDNA transcription.

• Why it matters: Dynamic nucleolar assembly is crucial for rDNA transcription and ribosome biogenesis, but how phosphorylation controls nucleolar architecture and Pol I function is not fully defined.
• What they did: Using super-resolution microscopy, domain mapping, phosphoproteomics, and structural modeling, the study shows PPM1D nucleolar localization via a C-terminal motif and targeting CK2 sites in TCOF1’s low-complexity repeat domain.
• The result: Loss of PPM1D or CK2 inhibition causes nucleolar disorganization and reduced rDNA transcription, and PPM1D inhibition sensitizes cells to RNA Pol I inhibitors in both p53-dependent and p53-independent contexts.

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