title: S-adenosyl homocysteine hydrolase is required for Myc-induced mRNA cap methylation, protein synthesis, and cell proliferation.
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.
authors.affiliation: Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Fernandez-Sanchez
authors.forename: Thomas
authors.initials: T
authors.lastname: Gonatopoulos-Pournatzis
authors.forename: Gavin
authors.initials: G
authors.lastname: Preston
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Lawlor
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Cowling
mesh_terms: D043383:Adenosylhomocysteinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D008745:Methylation; D051379:Mice; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012315:RNA Caps / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D043383:Adenosylhomocysteinase