Keeping the nucleolus a liquid condensate
The nucleolus is a multilayered, membraneless nuclear condensate in which DNA polymerase I (Pol I)–mediated ribosomal DNA (rDNA) transcription and pre-rRNA processing occur in fibrillar center and dense fibrillar component (FC/DFC) units. How the biophysical properties of the nucleolus are regulated has remained elusive. Wu et al. found that the RNA helicase DDX21 forms a shell coating each FC/DFC unit in the nucleolus (see the Perspective by Yamazaki and Hirose). The authors found that a long noncoding RNA called SLERT facilitates the transition from the open to the closed configuration of the helicase using a chaperonelike mechanism. DDX21 in the closed conformation forms loose clusters that confer the FC/DFC unit sufficient liquidity and space required for Pol I processivity. In addition, DDX21 within the loose clusters cannot approach and wrap rDNA, thus licensing rDNA for transcription.
Science, abf6582, this issue p. 547; see also abj8350, p. 486
Abstract
RNA polymerase I (Pol I) transcription takes place at the border of the fibrillar center (FC) and the dense fibrillar component (DFC) in the nucleolus. Here, we report that individual spherical FC/DFC units are coated by the DEAD-box RNA helicase DDX21 in human cells. The long noncoding RNA (lncRNA) SLERT binds to DDX21 RecA domains to promote DDX21 to adopt a closed conformation at a substoichiometric ratio through a molecular chaperone–like mechanism resulting in the formation of hypomultimerized and loose DDX21 clusters that coat DFCs, which is required for proper FC/DFC liquidity and Pol I processivity. Our results suggest that SLERT is an RNA regulator that controls the biophysical properties of FC/DFCs and thus ribosomal RNA production.