Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors.
Methylation of the mRNA 5' guanosine cap is essential for efficient gene expression. The 5' methyl cap binds to eIF4E, which is the first step in the recruitment of mRNA to the 40S ribosomal subunit. To investigate whether mRNA cap methylation is regulated in a gene-specific manner, we established a method to detect the relative level of cap methylation on specific mRNAs. We found that two transcription factors, c-Myc and E2F1, induce cap methylation of their transcriptional target genes, and therefore, c-Myc and E2F1 upregulate gene expression by simultaneously inducing transcription and promoting translation. c-Myc-induced cap methylation is greater than transcriptional induction for the majority of its target genes, indicating that this is a major mechanism by which Myc regulates gene expression.
Cole
M D
MD
Department of Pharmacology, Dartmouth Medical School, Lebanon, NH, USA.
Cowling
V H
VH
D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012315:RNA Caps; D012333:RNA, Messenger / Q000378:metabolism*; D015854:Up-Regulation
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D012333:RNA, Messenger