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Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways
Human mRNAs targeted by NMD show overlapping breakdown by two degradation pathways, SMG6 and SMG7
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Abstract
A combinatorial approach identified numerous NMD-targeted transcripts in human cells, revealing extensive redundancy between decay routes.
- Nonsense-mediated mRNA decay (NMD) not only degrades mRNAs with premature translation termination codons but also targets many normal mRNAs.
- The study combined transcriptome profiling of knockdowns and rescues of NMD factors UPF1, SMG6, and SMG7 to identify reliable NMD targets.
- SMG6 and SMG7 were found to act on essentially the same transcripts, suggesting redundancy in their function.
- In addition to mRNAs, many long noncoding RNAs and host genes for miRNAs and snoRNAs were identified as NMD targets.
- Key features predicting NMD targets include an intron in the 3' UTR, upstream open reading frames (uORFs), and long 3' UTRs.
- NMD-targeted transcripts tend to have higher GC content and are phylogenetically less conserved compared to NMD-insensitive transcripts.
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