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c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma.
Singh, Kamini; Lin, Jianan; Zhong, Yi; Burcul, Antonija; Mohan, Prathibha; Jiang, Man; Sun, Liping; Yong-Gonzalez, Vladimir; Viale, Agnes; Cross, Justin R; Hendrickson, Ronald C; Rätsch, Gunnar; Ouyang, Zhengqing; Wendel, Hans-Guido.
Afiliação
  • Singh K; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Lin J; The Jackson Laboratory for Genomic Medicine, Farmington, CT.
  • Zhong Y; Department of Biomedical Engineering, University of Connecticut, Storrs, CT.
  • Burcul A; Computational Biology Department, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Mohan P; Computational Biology Department, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Jiang M; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Sun L; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Yong-Gonzalez V; Integrated Genomics Operation, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Viale A; Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Cross JR; Integrated Genomics Operation, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Hendrickson RC; Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Rätsch G; Proteomics and Microchemistry, Memorial Sloan- Kettering Cancer Center, New York, NY.
  • Ouyang Z; Computational Biology Department, Memorial Sloan Kettering Cancer Center, New York, NY raetsch@inf.ethz.ch.
  • Wendel HG; Biomedical Informatics, Department of Computer Science, Swiss Federal Institute of Technology, Zürich, Switzerland.
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biossíntese de Proteínas / RNA Mensageiro / Proteínas Proto-Oncogênicas c-myc / Sítio de Iniciação de Transcrição / Linfoma Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biossíntese de Proteínas / RNA Mensageiro / Proteínas Proto-Oncogênicas c-myc / Sítio de Iniciação de Transcrição / Linfoma Idioma: En Ano de publicação: 2019 Tipo de documento: Article