Antisense oligonucleotide–directed inhibition of nonsense-mediated mRNA decay

Nonsense-mediated mRNA decay among coagulation factor genes

Objective(s): Haemostasis prevents blood loss following vascular injury. It depends on the unique concert of events involving platelets and specific blood proteins, known as coagulation factors. The clotting system requires precise regulation and coordinated reactions to maintain the integrity of the vasculature. Clotting insufficiency mostly occurs due to genetically inherited coagulation fact...

Nonsense-mediated mRNA 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...

Nonsense-mediated mRNA decay

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...

SnapShot: Nonsense-Mediated mRNA Decay

Nonsense-mediated decay of human HEXA mRNA.

Nonsense-mediated mRNA decay (NMD), the loss of mRNAs carrying premature stop codons, is a process by which cells recognize and degrade nonsense mRNAs to prevent possibly toxic effects of truncated peptides. Most mammalian nonsense mRNAs are degraded while associated with the nucleus, but a few are degraded in the cytoplasm; at either site, there is a requirement for translation and for an intr...