Nonsense-mediated RNA decay: a molecular system micromanaging individual gene activities and suppressing genomic noise

Nonsense-mediated RNA decay (NMD) is an evolutionary conserved system of RNA surveillance that detects and degrades RNA transcripts containing nonsense mutations. Given that these mutations arise at a relatively low frequency, are there any as yet unknown substrates of NMD in a wild-type cell? With this question in mind, Mendell et al.((1)) have used a microarray assay to identify those human genes under NMD regulation. Their results show that, in human cells, NMD regulates hundreds of physiologic transcripts and not just those containing nonsense mutations. Among the NMD targets are a number of non-functional RNAs expressed from vestigial sequences derived from retroviral and transposable elements. These findings support the notion that NMD is a high profile post-transcriptional mechanism micromanaging the activity of multiple gene batteries and suppressing the expression of genetic remnants.