Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells

Nonsense-mediated mRNA decay (NMD) generally involves nonsense codon recognition by translating ribosomes at a position ∼25 nts upstream of a splicing-generated exon junction complex of proteins. As such, NMD provides a means to degrade abnormal mRNAs that encode potentially deleterious truncated proteins. Additionally, an estimated one-third of naturally occurring, alternatively spliced mRNAs is also targeted for NMD. Given the extraordinary frequency of alternative splicing together with data indicating that naturally occurring transcripts other than alternatively spliced mRNAs are likewise targeted for NMD, it is believed that mammalian cells routinely utilize NMD to achieve proper levels of gene expression.