S-Adenosyl Homocysteine Hydrolase Is Required for Myc-Induced mRNA Cap Methylation, Protein Synthesis, and Cell Proliferation

Maria Elena Fernandez-Sanchez, Thomas Gonatopoulos-Pournatzis, Gavin Preston, Margaret A. Lawlor, Victoria H. Cowling (Lead / Corresponding author)

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    Abstract

    The c-Myc proto-oncogene promotes mRNA cap methylation, which is essential for almost all mRNA translation. The mRNA cap methylation reaction produces an inhibitory byproduct, S-adenosyl homocysteine. Here we report that Myc promotes upregulation of S-adenosyl homocysteine hydrolase (SAHH), an enzyme which hydrolyzes S-adenosyl homocysteine, thus neutralizing its inhibitory effects, and this is required for c-Myc-induced mRNA cap methylation. c-Myc-induced mRNA cap methylation was repressed by inhibiting the expression or activity of SAHH, whereas the same treatments did not have a significant effect on c-Myc-induced transcription or other c-Myc-dependent methylation events. The selective inhibition of mRNA cap methylation afforded by SAHH repression revealed that c-Myc-induced cap methylation could be correlated with the core c-Myc functions of protein synthesis, cell proliferation, and cell transformation.

    Original languageEnglish
    Pages (from-to)6182-6191
    Number of pages10
    JournalMolecular and Cellular Biology
    Volume29
    Issue number23
    DOIs
    Publication statusPublished - 1 Dec 2009

    Keywords

    • CARBOXY-TERMINAL DOMAIN
    • POLYMERASE-II
    • CAPPING ENZYME
    • C-MYC
    • ADENOSYLHOMOCYSTEINE HYDROLASE
    • GENOMIC TARGETS
    • XENOPUS-LAEVIS
    • TRANSCRIPTION
    • METHYLTRANSFERASE
    • TRANSLATION

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