MYC dependent mRNA translation shapes gene expression and cell biology

We report that MYC controls the translation of specific mRNAs in a sequence and RNA binding protein dependent manner. Specifically, using transcriptome-scale ribosome footprinting we identify 882 mRNAs whose translation depends on MYC. These mRNAs are highly significantly enriched for specific 5ÕUTR sequence motifs that bind the SRSF1/RBM42/HNRNPK complex. For example, MYC and SRFSF1/RBM42 dependent transcripts include many components of the electron transport chain and directly affect cellular respiration. Our results provide an integrated map of MYC driven gene expression programs that includes MYCÕs ability to control mRNA translation. Overall design: Human B-cell lymphoma P493 cells were treated with Tetracycline (0.1 uM) for 24 hrs followed by cycloheximide treatment for 10 minutes in triplicates. An aliquot of cells were used for total RNA preparation and remaining cells were processed for isolation of ribosome protected fragments.