Research Papers:

c-Myc deregulation induces mRNA capping enzyme dependency

Olivia Lombardi, Dhaval Varshney, Nicola M. Phillips and Victoria H. Cowling _

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Oncotarget. 2016; 7:82273-82288. https://doi.org/10.18632/oncotarget.12701

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Olivia Lombardi1, Dhaval Varshney1, Nicola M. Phillips1,2 and Victoria H. Cowling1

1 Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK

2 School of Science and the Environment, Manchester Metropolitan University, Manchester, M15 6BH, UK

Correspondence to:

Victoria H. Cowling, email:

Keywords: c-Myc, mRNA cap, transcription, translation, cell proliferation

Received: October 04, 2016 Accepted: October 10, 2016 Published: October 16, 2016


c-Myc is a potent driver of many human cancers. Since strategies for directly targeting c-Myc protein have had limited success, upstream regulators and downstream effectors of c-Myc are being investigated as alternatives for therapeutic intervention. c-Myc regulates transcription and formation of the mRNA cap, which is important for transcript maturation and translation. However, the direct mechanism by which c-Myc upregulates mRNA capping is unclear. mRNA cap formation initiates with the linkage of inverted guanosine via a triphosphate bridge to the first transcribed nucleotide, catalysed by mRNA capping enzyme (CE/RNGTT). Here we report that c-Myc increases the recruitment of catalytically active CE to RNA polymerase II and to its target genes. c-Myc-induced target gene expression, cell proliferation and cell transformation is highly dependent on CE, but only when c-Myc is deregulated. Cells retaining normal control of c-Myc expression are insensitive to repression of CE. c-Myc expression is also dependent on CE. Therefore, inhibiting CE provides an attractive route for selective therapeutic targeting of cancer cells which have acquired deregulated c-Myc.

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