Regulator of nonsense transcripts 1 (UPF1)

Is recruited to mRNAs upon translation termination and experiences a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD. Recruited by release factors to stalled ribosomes along with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1- eRF3) complicated.

In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (found 50-55 or more nucleotides downstream from the termination codon) via UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to supply a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to function as adapters to protein phosphatase 2A (PP2A), thus triggering UPF1 dephosphorylation and allowing the recycling of NMD factors.