rRNA transcription is integral to phase separation and maintenance of nucleolar structure

• DOI: 10.1371/journal.pgen.1010854
• Publication Date: 2023-08-28T17:35:26Z
• Authors: Soma Dash; Maureen C. Lamb; Jeffrey J. Lange; Mary C. McKinney; Dai Tsuchiya; Fengli Guo; Xia Zhao; Timothy J. Corbin; MaryEllen Kirkman; Kym Delventhal; Emma L. Moore; Sean McKinney; Rita Shiang; Paul A. Trainor
• Keywords: ribosome biogenesis; Transcription; RNA polymerase I; RNA polymerase III

Transcription of ribosomal RNA (rRNA) by Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which intimately tied to cell growth and proliferation. Perturbation biogenesis results tissue specific disorders termed ribosomopathies association with alterations nucleolar structure. However, how rRNA transcription regulate structure during normal development pathogenesis disease remains poorly understood. Here we show that homozygous null mutations Pol subunits required lead preimplantation lethality. Moreover, discovered Polr1a -/- , Polr1b Polr1c Polr1d mutants exhibit defects their nucleoli, as evidenced a decrease number precursor bodies concomitant increase volume, single condensed nucleolus. Pharmacological inhibition midgestation embryos, well hiPSCs, similarly or fragmented nucleoli. We find when function inhibited, viscosity granular compartment increases, disrupts its phase separation properties, leading if progresses through mitosis, absence prevents reassembly manifests Taken together, our data suggests are maintaining integrity disease.