Drosophila and human cell studies reveal a conserved role for CEBPZ, NOC2L and NOC3L in rRNA processing and tumorigenesis.

Abstract

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 CEBPZ, the 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 might promote tumor growth, whereas reduced expression could exert tumor-suppressive effects, underscoring their complex and unexpected regulatory roles in cancer.