Nonsense-mediated mRNA decay (NMD) mechanisms

Nonsense-mediated mRNA decay (NMD) is a translation-coupled mechanism that eliminates mRNAs containing premature translation-termination codons (PTCs). In mammalian cells, NMD is also linked to pre-mRNA splicing, as in many instances strong mRNA reduction occurs only when the PTC is located upstream of an intron. It is proposed that in these systems, the exon junction complex (EJC) mediates the link between splicing and NMD. Recent studies have questioned the role of splicing and the EJC in initiating NMD. Instead, they put forward a general and evolutionarily conserved mechanism in which the main regulator of NMD is the distance between a PTC and the poly(A) tail of an mRNA. Here we discuss the limitations of the new NMD model and the EJC concept; we argue that neither satisfactorily accounts for all of the available data and offer a new model to test in future studies.