Recent transcriptome-wide mapping of UPF1 binding sites reveals evidence for its recruitment to mRNA before translation

The ATP-dependent RNA helicase UPF1, a key factor in nonsense-mediated mRNA decay (NMD), was so far thought to be recruited specifically to NMD-targeted mRNAs by aberrantly terminating ribosomes. However, two recent publications reporting independently transcriptome-wide mapping of UPF1 occupancy on RNA challenge this model and instead provide evidence that UPF1 binds to mRNA already before translation. According to the new data, UPF1 appears to initially bind all mRNAs along their entire length and gets subsequently stripped off the coding sequence by translating ribosomes. This re-poses the question of where and how UPF1 engages with mRNA and how the NMD-targeted transcripts are selected among the UPF1-bound mRNAs.