Human mRNAs targeted by NMD show overlapping breakdown by two degradation pathways, SMG6 and SMG7

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.

Simplified