Myc up-regulates formation of the mRNA methyl cap

The Myc proteins c-Myc and N-Myc are essential for development and tissue homoeostasis. They are up-regulated by growth factors and transmit the signal for cell growth and proliferation. Myc proteins are also prominent oncogenes in many human tumour types. Myc proteins regulate the transcription of protein-encoding mRNAs and the tRNAs and rRNA which mediate mRNA translation into protein. Myc proteins also up-regulate translation by increasing addition of the 7-methylguanosine cap (methyl cap) to the 5' end of pre-mRNA. Addition of the methyl cap increases the rate at which transcripts are translated by directing RNA modifications and translation initiation. Myc induces methyl cap formation by promoting RNA polymerase II phosphorylation which recruits the capping enzymes to RNA, and by up-regulating the enzyme SAHH (S-adenosylhomocysteine hydrolase), which neutralizes the inhibitory by-product of methylation reactions. Myc-induced cap methylation is a major effect of Myc function, being necessary for activated protein synthesis, cell proliferation and cell transformation. Inhibition of cap methylation is synthetic lethal with elevated Myc protein expression, which indicates the potential for cap methylation to be a therapeutic target.