Mol. Cell https://doi.org/10.1016/j.molcel.2019.08.014 (2019)
The most abundant RNA components in cells are ribosomal (r)RNA, which are transcribed and processed within the nucleolus. However, the rapid processing of pre-rRNAs makes it challenging to study the underlying mechanisms. Using multiple high-resolution optical imaging approaches, Yao et al. found that pre-rRNA processing factors, including FBL, formed clusters in dense fibrillar components (DFC) surrounding the active rDNA and Pol I complex localized at the border of fibrillar centers of nucleoli. FBL underwent phase separation via self-association of its GAR domain and guided nascent 47S pre-rRNA into DFC through interaction with the 5′ terminus of pre-rRNA. The length of intrinsically disordered regions (IDRs) in GAR domains is correlated to its self-association ability and is associated with pre-rRNA processing. Interruption of the interaction between FBL and pre-rRNA impairs the formation of FBL clusters. Replacement of the GAR domain with different IDRs rescued FBL-knockout-induced abnormality in pre-rRNA sorting and processing. This study reveals the roles of IDRs in sub-organelle organization and deepens our understanding of connections between spatial organization and biological function.