Upregulation of 5'-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor.

ABSTRACT: Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5'-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increase

SUBMITTER: Cottrell KA 

PROVIDER: S-EPMC7747592 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature