TY - JOUR
T1 - C-MYC regulates mRNA translation efficiency and start-site selection in lymphoma
AU - Singh, Kamini
AU - Lin, Jianan
AU - Zhong, Yi
AU - Burčul, Antonija
AU - Mohan, Prathibha
AU - Jiang, Man
AU - Sun, Liping
AU - Yong-Gonzalez, Vladimir
AU - Viale, Agnes
AU - Cross, Justin R.
AU - Hendrickson, Ronald C.
AU - Rätsch, Gunnar
AU - Ouyang, Zhengqing
AU - Wendel, Hans Guido
N1 - Publisher Copyright:
© 2019 Singh et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20181726
DO - 10.1084/jem.20181726
M3 - Article
C2 - 31142587
AN - SCOPUS:85069265624
SN - 0022-1007
VL - 216
SP - 1509
EP - 1524
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -