PT  - JOURNAL ARTICLE
AU  - Joshua A. Riback
AU  - Jorine M. Eeftens
AU  - Daniel S. W. Lee
AU  - Sofia A. Quinodoz
AU  - Lien Beckers
AU  - Lindsay A. Becker
AU  - Clifford P. Brangwynne
TI  - Viscoelastic RNA entanglement and advective flow underlie nucleolar form and function
AID  - 10.1101/2021.12.31.474660
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.12.31.474660
4099  - http://biorxiv.org/content/early/2022/01/02/2021.12.31.474660.short
4100  - http://biorxiv.org/content/early/2022/01/02/2021.12.31.474660.full
AB  - The nucleolus facilitates transcription, processing, and assembly of ribosomal RNA (rRNA), the most abundant RNA in cells. Nucleolar function is facilitated by its multiphase liquid properties, but nucleolar fluidity and its connection to ribosome biogenesis remain unclear. Here, we used quantitative imaging, mathematical modeling, and pulse-chase nucleotide labelling to map nucleolar rRNA dynamics. Inconsistent with a purely diffusive process, rRNA steadily expands away from the transcriptional sites, moving in a slow (~1Å/s), radially-directed fashion. This motion reflects the viscoelastic properties of a highly concentrated gel of entangled rRNA, whose constant polymerization drives steady outward flow. We propose a new viscoelastic rRNA release model, where nucleolar rRNA cleavage and processing reduce entanglement, fluidizing the nucleolar periphery to facilitate release of mature pre-ribosomal particles.Competing Interest StatementCPB is a founder and consultant for Nereid Therapeutics