microRNA/Argonaute 2 regulates nonsense-mediated messenger RNA decay

Imperfect base‐pairing between microRNA (miRNA) and the 3′‐untranslated region of target messenger RNA (mRNA) triggers translational repression of the target mRNA. Here, we provide evidence that human Argonaute 2 targets cap‐binding protein (CBP)80/20‐bound mRNAs and exon junction complex‐bound mRNAs and inhibits nonsense‐mediated mRNA decay (NMD), which is restricted tightly to CBP80/20‐bound mRNAs. Furthermore, microarray analyses reveal that a subset of cellular transcripts, which are expected to be targeted for NMD, is stabilized by miRNA‐mediated gene silencing. The regulation of NMD by miRNAs will shed light on a new post‐transcriptional regulation mechanism of gene expression in mammalian cells. Kim and colleagues provide evidence that Ago2 targets CBP80/20‐ and EJC‐bound mRNAs and inhibits their nonsense‐mediated mRNA decay (NMD). They also show that a subset of transcripts expected to be targeted for NMD are stabilized by miRNA‐mediated gene silencing. The crosstalk between NMD and miRNA‐mediated gene silencing sheds light on a new post‐transcriptional regulation mechanism in mammalian cells.