Master of disguise: ribosomal protein L5 beyond translation

Ribosomal proteins (RPs), key components of ribosomes, are traditionally associated with protein synthesis. However, emerging evidence suggests their involvement in diverse cellular functions beyond ribosomal biogenesis and translation, including transcriptional regulation. This study aimed at investigating the potential of RPs as transcriptional regulators by analyzing their interacting protein network. A subset of RP interactors exhibiting transcriptional regulatory functions was subjected to Gene Ontology analysis to identify enriched functional pathways. The results indicated that these interactions may play a role in different cellular pathways relevant to a number of biological processes, including cancer. To further explore this hypothesis, a virtual knockdown of RPL5 was performed in ovarian and breast cancer public data. As proof of concept the same experiments were conducted in vitro to validate the computational findings, confirming the potential of RPL5 in transcriptional regulation in cancer. This seminal study provides a foundation for future investigations into the multifaceted roles of RPs in the regulation of gene expression in physiological and pathological contexts.