Cutting the nonsense: the degradation of PTC-containing mRNAs

In eukaryote s mRNAs harbouring PTCs (premature translation termination codons) arc recognized and eliminated by NMD (nonsense mediated mRNA decay) In addition to its quality control function NMD constitutes 3 translation dependent post transcriptional pathway to regulate the expression levels of physiological mRNAs In contrast with PTC recognition little is known about the mechanisms that trigger the rapid degradation of mammalian nonsense mRNA Studies have shown that mammalian NMD targets can be degraded via both an SMG6 (where SMG is suppressor of morphological defects on genitalia) dependent endonucleolytic pathway and a deadenylation and decapping dependent exonucleolytic pathway with the possible involvement of SMG5 and SMG7 In contrast Drosophila melanogaster NMD is confined to the former find Saccharomyces cerevisiae NMD to the latter decay pathway Consistent with this conclusion mammals possess both SMG6 and SMG7 whereas D melanogaster lacks an SMG7 homologue and yeast have no SMG6 equivalent In the present paper we review what is known about the degradation of PTC containing mRNAs so far paying particular attention to the properties of the NMD specific factors SMG5-SMG7 and to what is known about the mechanism of degrading mRNAs after they have been committed to the NMD pathway