Overexpression of the c-myc oncogene inhibits nonsense-mediated RNA decay in B lymphocytes.

The Myc transcription factor plays a vital role in both normal cellular physiology and in many human cancers. We have recently demonstrated that nonsense-mediated RNA decay (NMD), a mechanism that rapidly degrades select mRNAs, is inhibited by the stress-induced phosphorylation of translation initiation factor eIF2α, and this inhibition stabilizes many transcripts necessary for tumorigenesis. Here, we demonstrate that NMD is inhibited by high Myc expression. We show that the phosphorylation of eIF2α, likely due to the ability of Myc to generate reactive oxygen species and augment endoplasmic reticulum stress, is necessary for the inhibition of NMD by Myc. The inhibition of NMD both stabilizes and up-regulates multiple Myc targets, suggesting that the inhibition of NMD may play an important role in the dynamic regulation of genes by Myc.