c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma.
Document Type
Article
Publication Date
7-1-2019
Keywords
JGM
JAX Source
J Exp Med 2019 Jul 1; 216(7):1509-1524
Volume
216
Issue
7
First Page
1509
Last Page
1524
ISSN
1540-9538
PMID
31142587
DOI
https://doi.org/10.1084/jem.20181726
Grant
CA034196,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.
Recommended Citation
Singh K,
Lin J,
Zhong Y,
Burčul A,
Mohan P,
Jiang M,
Sun L,
Yong-Gonzalez V,
Viale A,
Cross J,
Hendrickson R,
Rätsch G,
Ouyang Z,
Wendel H.
c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma. J Exp Med 2019 Jul 1; 216(7):1509-1524