NudC moonlights in ribosome biogenesis and homeostasis in polyploid cells of Drosophila melanogaster

Ribosomes, the cellular machinery responsible for protein synthesis, are fundamental across all kingdoms of life. Disruption of ribosome biogenesis (RiBi) can cause severe ribosomopathies, underscoring the need for precise regulatory mechanisms. In this study, we identified a role for the gene nuclear distribution C, dynein complex regulator (NudC) in RiBi within polyploid cells of Drosophila melanogaster larvae. Depletion of NudC in polyploid salivary gland cells led to a significant reduction in ribosome abundance, accompanied by the loss of ribosome-binding sites on the rough endoplasmic reticulum and impaired translation. These defects are linked to decreased ribosomal RNA levels. Notably, NudC knockdown also triggered a homeostatic response, characterized by increased transcription and translation of ribosome biogenesis factors and ribosomal proteins. This response is similar to that observed in cells with defective ribosomal activity, suggesting that the ribosomal impairment triggers transcriptional feedback to maintain ribosome function. Meanwhile, NudC-deficient cells exhibited chromosome abnormalities, JNK signalling activation and autophagy—resembling defects from ribosome dysfunction. Finally, our findings suggest that the role of NudC in RiBi is independent of its established function in dynein regulation, indicating its moonlighting role in RiBi. Together, these results uncover a new, fundamental function for NudC in maintaining RiBi and homeostasis in polyploid cells.