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The Journal of Experimental Medicine
Article . 2019 . Peer-reviewed
License: CC BY NC SA
Data sources: Crossref
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The Journal of Experimental Medicine
Article
License: CC BY NC SA
Data sources: UnpayWall
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Research Collection
Article . 2019
License: CC BY NC SA
ETH Zürich Research Collection
Article . 2019
License: CC BY NC SA
Data sources: Datacite
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c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma

Authors: Kamini Singh; Jianan Lin; Yi Zhong; Antonija Burčul; Prathibha Mohan; Man Jiang; Liping Sun; +7 Authors

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

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.

Keywords

570, JGM, Lymphoma, Life Sciences, 610, RNA-Binding Proteins, Proto-Oncogene Proteins c-myc, Open Reading Frames, Cell Line, Tumor, Protein Biosynthesis, Medicine and Health Sciences, Humans, RNA, Messenger, Transcription Initiation Site, 5' Untranslated Regions, Research Articles

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    38
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
38
Top 10%
Top 10%
Top 10%
Green
hybrid