A protein complex deposited upstream of exon-exon junctions after pre-mRNA splicing may serve a dual role in mRNA quality control by directing mRNA nuclear export and, possibly, serving as a downstream 'mark' for nonsense-mediated decay.

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved mRNA surveillance system that degrades mRNA transcripts that harbour a premature translation-termination codon (PTC), thus reducing the synthesis of truncated proteins that would otherwise have deleterious effects. Although extensive research has identified a conserved repertoire of NMD factors, these studies have been performed ...

Recent advances have led to a new understanding of how mRNAs are exported from the nucleus to the cytoplasm. This process requires a heterodimeric mRNA export receptor that is part of an elaborate machinery conserved from yeast to humans. Export of mRNAs is coupled to upstream steps in gene expression, such as pre-mRNA splicing, and to downstream events, including nonsense-mediated decay.

Translation and mRNA decay are coupled processes; the link is most obvious in the case of NMD (nonsense-mediated mRNA decay). NMD is a mechanism that drastically reduces the level of mRNA harbouring PTCs (premature translation termination codons). The defining event in NMD is premature translation termination and the key question is: what distinguishes premature from normal translation terminat...

Is it important? Absolutely! NMD probably evolved to eliminate abnormal transcripts due to routine errors in gene expression. For example, inefficient or inaccurate pre-mRNA splicing can generate an intron-derived in frame nonsense codon, or a shift in the reading frame and an exon-derived nonsense codon downstream of the shift. There are also natural substrates for NMD such as alternatively sp...