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

Kamini Singh, Jianan Lin, 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, Hans Guido Wendel

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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 59UTR 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.

Original languageEnglish (US)
Pages (from-to)1509-1524
Number of pages16
JournalJournal of Experimental Medicine
Issue number7
StatePublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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