Intranuclear degradation of nonsense codon‐containing mRNA

Intranuclear degradation of nonsense codon-containing mRNA.

Most vertebrate mRNAs with premature termination codons (PTCs) are specifically recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD) while still associated with the nucleus. However, it is still a matter of debate whether PTCs can be identified by intranuclear scanning or only by ribosomes on the cytoplasmic side of the nuclear envelope. Here we show that inhib...

CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected...

CYP3A5 mRNA degradation by nonsense mediated mRNA decay (NMD)

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...