c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma.
J Exp Med
; 216(7): 1509-1524, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31142587
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.
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Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
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RNA Mensageiro
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Proteínas Proto-Oncogênicas c-myc
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Sítio de Iniciação de Transcrição
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Linfoma
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article