The emerging role of RNA polymerase I transcription machinery in human malignancy: a clinical perspective

Abstract

Lorenzo Montanaro, Davide Treré, Massimo Derenzini Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy Abstract: Ribosome biogenesis – the complex and highly coordinated cellular process leading to the production of ribosomes – is strictly dependent on the activity of RNA polymerase I (Pol I) transcriptional machinery. Pol I activity is continually increased in proliferating cells to sustain the increased demand for ribosome production and protein synthesis, which are necessary for appropriate cell growth and division. The integrity of the process of ribosome biogenesis represents an important sensor of cellular stress: when this process is altered, a tumor suppressor response is triggered, which leads to proliferative arrest. The present review focuses on the possible implications of Pol I targeting in the treatment of human malignancies. Keywords: RNA polymerase I inhibitors, ribosome biogenesis, cell cycle control, cancer, Pol I