Myc regulation of mRNA cap methylation

Victoria H. Cowling, Michael D. Cole

    Research output: Contribution to journalReview article

    18 Citations (Scopus)

    Abstract

    The c-myc proto-oncogene regulates the expression of 15% to 20% of all genes, depending on the cell type, and the regulation is usually odest (1.5- to 2.0-fold). The authors discovered that in addition to regulating mRNA abundance, c-Myc regulates the formation of the 7-methylguanosine cap on many mRNAs, including transcriptional target genes and others not transcriptionally activated. Because the 7-methylguanosine cap is required for effective translation, enhanced methyl cap formation leads to increased protein production from Myc-responsive genes that exceeds the transcriptional induction. Increased cap methylation is linked to Myc-dependent enhanced activity of 2 critical kinases, TFIIH and p-TEFb, which phosphorylate the RNA polymerase II carboxy-terminal domain (CTD). Phosphorylation of the CTD recruits RNGTT and RNMT, the enzymes involved in mRNA capping, to the nascent transcript. Evidence is accumulating that enhanced cap methylation makes a significant contribution to Mycdependent gene regulation and protein production.
    Original languageEnglish
    Pages (from-to)576-579
    Number of pages4
    JournalGenes and Cancer
    Volume1
    Issue number6
    DOIs
    Publication statusPublished - Jun 2010

    Keywords

    • Myc
    • Gene expression
    • Translation
    • Cap methylation
    • Cell proliferation

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