From Flies to Humans: A Conserved Role of CEBPZ, NOC2L, and NOC3L in rRNA Processing and Tumorigenesis.

NOC1, NOC2, and NOC3 are evolutionarily conserved nucleolar proteins that play an essential role in the maturation and processing of ribosomal RNA (rRNA). NOC1, in Drosophila is necessary to sustain rRNA processing, whereas its depletion leads to impaired polysome formation, reduced protein synthesis, and induces apoptosis. In this study, we demonstrated that the RNA-regulatory functions of NOC1 are conserved in vertebrates, where the reduction of the CEBPZ homolog of NOC1 leads to the accumulation of unprocessed 45S pre-rRNA, a reduction in protein synthesis, and inhibition of cell growth. Gene Ontology and bioinformatic analyses of CEBPZ, NOC2L, and NOC3L in tumors highlight a significant correlation between their expression and processes that regulate rRNA processing and ribosomal maturation. Moreover, comparative analysis of TCGA datasets from tumor databases revealed that CEBPZ, NOC2L, and NOC3L exhibit contrasting expression patterns across tumor types. This context-dependent behavior suggests that overexpression of these proteins may promote tumor growth, whereas reduced expression could exert tumor-suppressive effects, underscoring their complex and unexpected regulatory roles in cancer. Summary StatementNOC1, NOC2, and NOC3 are conserved nucleolar proteins essential for rRNA processing. Their reduction impairs rRNA maturation, decreases protein synthesis, and induces cell death. CEBPZ, NOC2L, and NOC3L show context-dependent expression in tumors, suggesting dual roles in cancer progression and suppression.