Influence of perturbed ribosome assembly on transcription and pre-mRNA splicing in crosstalk with the oncogenes MDM2 and MDM4 (P08)

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This project addresses the impact of dysbalanced ribosome assembly on transcription and splicing, with a focus on the tumor suppressor p53 and its antagonists MDM2 and MDM4. We have observed that a complex of the 5S RNP and the MDM2 oncoprotein limits the activity of RNA Polymerase III to synthesize 5S rRNA. Moreover, the ribosomal protein eL22/RPL22 binds a specific stem-loop structure within intronic RNA to induce exon skipping of the MDM4 mRNA. We will explore how these regulatory mechanisms affect global gene expression and splicing patterns, and the synthesis of ribosome components.