Nascent ribosomal RNA acts as surfactant that suppresses growth of fibrillar centers in nucleolus

Liquid-liquid phase separation (LLPS) has been thought to be the assembly mechanism of the multiphase structure of nucleolus, the site of ribosomal biogenesis. Condensates assembled by LLPS increase their size to minimize the surface energy as far as their components are available. However, multiple microphases, fibrillar centers (FCs), dispersed in a nucleolus are stable and their size does not grow unless the transcription of pre-ribosomal RNA (pre-rRNA) is inhibited. To understand the mechanism of the suppression of the growth of FCs, we here construct a minimal theoretical model by taking into account the nascent pre-rRNA transcripts tethered to the surfaces of FCs by RNA polymerase I. Our theory predicts that nascent pre-rRNA transcripts generate the lateral osmotic pressure that counteracts the surface tension of the microphases and this suppresses the growth of the microphases over the optimal size. The optimal size of the microphases decreases with increasing the transcription rate and decreasing the rate of RNA processing. This prediction is supported by our experiments showing that the size of FCs increased with increasing the dose of transcription inhibitor. This theory may provide insight in the general mechanism of the size control of nuclear bodies.