Title

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

Document Type

Article

Publication Date

5-29-2019

Keywords

JGM

JAX Source

J Exp Med 2019 May 29; [Epub ahead of print]

PMID

31142587

DOI

https://doi.org/10.1084/jem.20181726

Grant

GM124998,CA08748

Abstract

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.

Share

COinS