The role of nucleotide composition in premature termination codon recognition.

We found that none of the known NMD-triggering features, such as the presence of upstream open reading frames, significantly characterizes EJC-independent NMD-targets. Instead, we saw that NMD-targets are strongly enriched with G nucleotides upstream of the termination codon, and even more so along their 3'UTR. We suggest that high G content around the termination codon impedes translation termination as a result of mRNA folding, thus triggering NMD. We also suggest that high G content in the 3'UTR helps to activate NMD by allowing for the accumulation of UPF1, or other NMD-promoting proteins, along the 3'UTR.