UPF protein

A member of the UPF surveillance-factor system. Artificial recruitment downstream of a termination codon can trigger nonsense-mediated decay when the required downstream machinery is present.

UPF3 is a conserved factor associated with nonsense-mediated decay. In mammalian exon-junction-linked surveillance, UPF3 proteins can connect an exon-junction-associated assembly with UPF2 and downstream UPF1-dependent events. Human paralogues UPF3A and UPF3B differ in context and activity, so the generic label should not imply identical contributions in every cell. Artificial tethering experiments helped establish that positioning UPF factors downstream of a termination codon can promote decay. ^[ref]

UPF2 is an adaptor protein in nonsense-mediated decay that interacts with UPF1 and UPF3. These interactions help couple the context of an RNA-protein assembly to activation of the decay pathway. The role is regulatory and organizational rather than simply recognizing a particular three-base stop codon in isolation. Different substrates can depend differently on individual surveillance components. ^[ref]

UPF1 is an ATP-dependent RNA helicase and central regulatory factor in nonsense-mediated decay. Its nucleotide cycle, interactions and phosphorylation help couple recognition of an inappropriate termination context to RNA remodelling and degradation. UPF2 can regulate its activity, while other factors recruit downstream decay functions. Because UPF1 also participates in additional RNA processes, a perturbation phenotype is not automatically attributable to one decay pathway alone. ^[ref]