c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma
c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma
The oncogenic c-MYC (MYC) transcription factor has broad effects on gene expression and cell behavior. We show that MYC alters the efficiency and quality of mRNA translation into functional proteins. Specifically, MYC drives the translation of most protein components of the electron transport chain in lymphoma cells, and many of these effects are independent from proliferation. Specific interactions of MYC-sensitive RNA-binding proteins (e.g., SRSF1/RBM42) with 5′UTR sequence motifs mediate many of these changes. Moreover, we observe a striking shift in translation initiation site usage. For example, in low-MYC conditions, lymphoma cells initiate translation of the CD19 mRNA from a site in exon 5. This results in the truncation of all extracellular CD19 domains and facilitates escape from CD19-directed CAR-T cell therapy. Together, our findings reveal MYC effects on the translation of key metabolic enzymes and immune receptors in lymphoma cells.
- University of Connecticut United States
- University of Connecticut Health Center United States
- ETH Zurich Switzerland
- Swiss Federal Insitute of Technology Switzerland
- Memorial Sloan Kettering Cancer Center United States
570, JGM, Lymphoma, Life Sciences, 610, RNA-Binding Proteins, Proto-Oncogene Proteins c-myc, Open Reading Frames, Cell Line, Tumor, Protein Biosynthesis, Medicine and Health Sciences, Humans, RNA, Messenger, Transcription Initiation Site, 5' Untranslated Regions, Research Articles
570, JGM, Lymphoma, Life Sciences, 610, RNA-Binding Proteins, Proto-Oncogene Proteins c-myc, Open Reading Frames, Cell Line, Tumor, Protein Biosynthesis, Medicine and Health Sciences, Humans, RNA, Messenger, Transcription Initiation Site, 5' Untranslated Regions, Research Articles
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