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Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors

Oncogene volume 28, pages 1169–1175 (2009)Cite this article

Abstract

Methylation of the mRNA 5′ guanosine cap is essential for efficient gene expression. The 5′ methyl cap binds to eIF4E, which is the first step in the recruitment of mRNA to the 40S ribosomal subunit. To investigate whether mRNA cap methylation is regulated in a gene-specific manner, we established a method to detect the relative level of cap methylation on specific mRNAs. We found that two transcription factors, c-Myc and E2F1, induce cap methylation of their transcriptional target genes, and therefore, c-Myc and E2F1 upregulate gene expression by simultaneously inducing transcription and promoting translation. c-Myc-induced cap methylation is greater than transcriptional induction for the majority of its target genes, indicating that this is a major mechanism by which Myc regulates gene expression.

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Acknowledgements

We thank Klara Acs for much helpful advice. We thank Kristian Helin for the E2F1-ER construct. This study was funded by NIH grants to MDC and an MRC grant to VHC.

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Authors and Affiliations

  1. Department of Pharmacology, Dartmouth Medical School, Lebanon, NH, USA

    M D Cole

  2. Department of Genetics, Dartmouth Medical School, Lebanon, NH, USA

    M D Cole

  3. Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee, UK

    V H Cowling

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  1. M D Cole
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  2. V H Cowling
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Correspondence to V H Cowling.

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Cole, M., Cowling, V. Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors. Oncogene 28, 1169–1175 (2009). https://doi.org/10.1038/onc.2008.463

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