Ribosomal protein uL3 status affects translation efficiency in colorectal cancer cells

mRNA translation is critical for gene expression regulation (1). A growing body of evidence suggests that changes in translational efficiency help activate key oncogenic signaling pathways. Translational control of specific subsets of mRNAs, in particular, promotes cancer cell survival and invasion, as well as chemotherapeutic resistance (2, 3). Ribosomal protein L3 (uL3) is a component of cytosolic ribosomes that plays a crucial role for both ribosome structure and function. Our research group has identified uL3 as stress sensing molecule essential for cellular response to certain chemotherapeutics in colorectal cancer cells lacking functional p53 (4,5). Specifically, uL3 status is associated with chemoresistance, epithelial-mesenchymal transition program alteration, increased cell migration and proliferation, inhibition of apoptosis, enhancement of autophagy, and overexpression of drug efflux transporters (6-9). The goal of this study was to determine the role of uL3 in the regulation of translational efficiency in p53-depleted colorectal cancer cells and a derivative cell line stably silenced for uL3 and resistant to 5-FU. The influence of uL3 on “translatome” and associated mRNAs has been investigated by using polysome profiling technique and qPCR analysis of ribosome-associated mRNAs. Results from these experiments will be presented.