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Updated: May 30, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

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

Guglielmo Rambaldelli1, Valeria Manara2, Andrea Vutera Cuda2

  • 1Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.

Biorxiv : the Preprint Server for Biology
|January 27, 2025
PubMed

Insights

Nucleolar proteins NOC1, NOC2, and NOC3 regulate ribosomal RNA (rRNA) maturation. Their vertebrate homologs, CEBPZ, NOC2L, and NOC3L, impact protein synthesis and have dual roles in cancer, affecting tumor growth and suppression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Biology

Background:

  • NOC1, NOC2, and NOC3 are conserved nucleolar proteins vital for ribosomal RNA (rRNA) maturation and cellular homeostasis.
  • Dysregulation of these proteins can impair protein synthesis and lead to apoptosis.

Purpose of the Study:

  • To investigate the conserved RNA-regulatory functions of vertebrate homologs CEBPZ, NOC2L, and NOC3L.
  • To explore the role of these proteins in cancer and their correlation with rRNA and ribosomal subunit maturation.

Main Methods:

  • Utilized Gene Ontology and bioinformatic analyses.
  • Analyzed tumor databases to compare expression patterns of CEBPZ, NOC2L, and NOC3L.

Main Results:

  • Demonstrated conserved RNA-regulatory functions of CEBPZ in vertebrates, leading to 45S pre-rRNA accumulation and reduced protein synthesis.
  • Identified significant correlations between reduced CEBPZ, NOC2L, and NOC3L expression and impaired rRNA and 60S ribosomal maturation in tumors.
  • Observed contrasting expression patterns of CEBPZ, NOC2L, and NOC3L across different tumor types.

Conclusions:

  • CEBPZ, NOC2L, and NOC3L play dual roles in cancer, with potential tumor-suppressive effects upon reduced expression and roles in promoting tumor growth upon overexpression.
  • These proteins exhibit unexpected regulatory functions in cancer, influencing tumor progression through rRNA and protein synthesis pathways.
Keywords:
CEBPZCancerDrosophilaEvolutionary conservationNOC1/2/3NOC2L/3LNucleolar proteinsRibosome biogenesisrRNA processing

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