FuHsi maintains nucleolar integrity

The nucleolus is a dynamic, membrane-less organelle that assembles around ribosomal DNA (rDNA) repeats and governs ribosome biogenesis. Its structural organization is tightly linked to its function. In our previous work, we identified FuHsi as a novel rDNA transcriptional regulator. However, its role in nucleolar architecture remains unknown. Here, we show that FuHsi co-localizes with UBF, RPA194, TCOF1, and rDNA, and is encapsulated by FBL and NPM1. Knockdown of FuHsi leads to the coordinated loss of these components from the nucleolus and uniquely causes rDNA to disperse into the nucleoplasm—a phenotype not observed upon TCOF1 depletion. Notably, TCOF1 knockdown displaces UBF but not FuHsi and rDNA, while UBF or RPA194 knockdown leads to peripheral redistribution of FuHsi. These data suggest that FuHsi functions upstream of TCOF1 and UBF and is required for anchoring rDNA at the nucleolar core. We propose that FuHsi functions at the top of the nucleolar assembly cascade and identifies a novel initiation step critical for rDNA organization and nucleolar formation.