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Enhanced mRNA cap methylation increases Cyclin D1 expression and promotes cell transformation

Oncogene volume 29, pages 930–936 (2010)Cite this article

Abstract

Cap-dependent mRNA translation requires the methylation of the mRNA guanosine cap by RNA guanine-7-methyltransferase (RNMT). mRNA cap methylation was recently described to be rate-limiting for a subset of mRNAs, and to be enhanced by expression of c-Myc and E2F1, although the biological significance of this finding was not investigated. Here, it is reported that increased RNMT expression enhances cellular mRNA cap methyltransferase activity, promotes mammary epithelial cell transformation and cooperates with H-RasV12 or c-Myc to promote fibroblast cell transformation. Cyclin D1 is a prominent oncogene in epithelial tumours. A significant fraction of Cyclin D1 mRNA was found to be unmethylated on the mRNA cap and thus dormant in mammary epithelial cells. Cyclin D1 expression was increased by enhanced mRNA cap methylation. In summary, this report shows that mRNA cap methylation is rate-limiting for expression of an oncogene and cell transformation.

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Acknowledgements

I thank Mike Cole for the generous gift of the anti-m7G antibodies, Aaron Shatkin for providing the RNMT-GFP construct, Julian Downward for providing the H-RasV12 construct and James DiRenzo for providing IMEC. I also thank all of the above and the Cowling lab for advice. This work was funded by an MRC Career Development Award and a Tenovus Scotland Project Grant.

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

    V H Cowling

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Correspondence to V H Cowling.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Cowling, V. Enhanced mRNA cap methylation increases Cyclin D1 expression and promotes cell transformation. Oncogene 29, 930–936 (2010). https://doi.org/10.1038/onc.2009.368

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