ARF suppresses 5’-terminal oligopyrimidine mRNA translation

Abstract

6Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As 7 such, tumor cells must acquire enhanced ribosome production. How many of the mutations in tumor cells 8 ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly 9 deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and 10 processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we 11 show that ARF is a major suppressor of 5'-terminal oligopyrimidine mRNA translation. Genes with increased 12 translational efficiency following loss of ARF include many ribosomal proteins and translation factors. 13 Knockout of p53 caused a similar increase in 5'-TOP mRNA translation. The 5'-TOP regulators mTORC1, eIF4G1 14 and LARP1 are dysregulated in ARF and p53 null cells. 15 16 17 18