Nonsense‐mediated decay of glutathione peroxidase 1 mRNA in the cytoplasm depends on intron position

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Abstract
MRNA for glutathione peroxidase 1 (GPx1) is subject to cytoplasmic nonsense‐mediated decay (NMD) when the UGA selenocysteine (Sec) codon is recognized as nonsense. Here, we demonstrate by moving the sole intron of the GPx1 gene that either the Sec codon or a TAA codon in its place elicits NMD when located ≥59 bp but not ≤43 bp upstream of the intron. Therefore, the exon–exon junction of GPx1 mRNA positions the boundary between nonsense codons that do and do not elicit NMD, as has been shown for the 3′‐most junctions of mRNAs subject to nucleus‐associated NMD. We also demonstrate by using a regulatable promoter to drive GPx1 gene expression that cytoplasmic NMD is characteristic of steady‐state mRNA, in contrast to nucleus‐associated NMD. These findings clarify the mechanistic relationship between cytoplasmic and nucleus‐associated NMD and offer the first demonstration that nuclear introns can influence cytoplasmic NMD. Finally, by analyzing hybrid GPx1 genes, we disprove the idea that the cellular site of NMD is determined by the efficiency of translation initiation.

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