Tissue-specific RNA surveillance? Nonsense-mediated mRNA decay causes collagen X haploinsufficiency in Schmid metaphyseal chondrodysplasia cartilage

Abstract

Mutations resulting in a premature termination codon (PTC) are a major cause of inherited disorders, and the majority of these mutant RNA transcripts are subjected to nonsense-mediated mRNA decay (NMD). This RNA surveillance results in reduced mutant allele expression, the extent of which can impact on the clinical severity. The molecular mechanisms of NMD in mammalian cells, its relationship to splicing and translation, downstream sequence elements and binding factors remains only partially understood. Currently there is little information on whether the extent of NMD is gene- or tissue-specific, although nonsense mutation inhibition of RNA splicing has been shown to exhibit some tissue and..