# Noc1 downregulation induces nucleolar stress and upregulates p53 isoforms, with a robust increase of the truncated p53E isoform in Drosophila wing discs

## TL;DR

Reducing Noc1 in fruit fly wing cells causes nucleolar stress, increases p53 levels, and especially boosts a specific p53 isoform called p53E.

## Contribution

The study identifies p53E as a robustly upregulated isoform during nucleolar stress in Drosophila.

## Key findings

- Noc1 depletion in Drosophila wing discs causes nucleolar stress and increases p53 levels.
- The p53E isoform is significantly upregulated compared to other p53 isoforms.
- γ-H2AV accumulation is linked to caspase-dependent apoptosis, not DNA damage.

## Abstract

Disruption of ribosome biogenesis triggers nucleolar stress, a conserved cellular response that activates p53. We previously demonstrated that depletion of Nucleolar Complex Protein 1 (Noc1) in Drosophila wing imaginal discs impairs rRNA maturation and ribosome assembly, resulting in elevated p53 levels and apoptosis, hallmarks of nucleolar stress. The Drosophila p53 gene produces four mRNA isoforms, yet their individual contributions to nucleolar stress responses remain poorly understood. Using newly designed isoform-specific qPCR primers, we found that although all p53 isoforms exhibit moderate transcriptional changes following Noc1 reduction, the truncated isoform p53E is robustly and preferentially upregulated. Notably, p53E lacks the N-terminal transactivation domain and has been reported to negatively regulate p53-induced apoptosis in specific tissues. Furthermore, our analyses indicate that γ-H2AV accumulation arises from caspase-dependent apoptosis rather than primary genomic lesions, suggesting the activation of a p53-dependent stress pathway distinct from canonical genotoxic pathways. Together, these findings suggest that p53E may be part of a novel mechanism activated during nucleolar stress, providing insight into how cells adapt to defects in ribosome biogenesis.