A phase-separating microprotein partitions DDX21 to coordinate nucleolar transcription and rRNA processing

Here, we identify TaYü, a 148–amino-acid microprotein encoded by the annotated lncRNA SLC12A5-AS1, as a key regulator of nucleolar compartmentalization. TaYü promotes ribosome biogenesis by partitioning the RNA helicase DDX21 to rDNA, thereby enhancing RNA polymerase I–dependent transcription while restricting its over participation in RNA polymerase II–associated programs.

In parallel, TaYü promotes the assembly of DDX21 with fibrillarin and U3 snoRNA to couple rRNA processing. Mechanistically, TaYü undergoes phase separation and co-condenses with DDX21 and rDNA to organize nucleolar transcriptional hubs. Functionally, TaYü is upregulated in cancer and supports tumor growth.