c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma.

Kamini Singh
Jianan Lin, The Jackson Laboratory
Yi Zhong
Antonija Burčul
Prathibha Mohan
Man Jiang
Liping Sun
Vladimir Yong-Gonzalez
Agnes Viale
Justin R Cross
Ronald C Hendrickson
Gunnar Rätsch
Zhengqing Ouyang, The Jackson Laboratory
Hans-Guido Wendel


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.