InterPro domain: IPR018999

UPF1 (or regulator of nonsense transcripts 1 homologue) is an essential RNA helicase that detects mRNAs containing premature stop codons and triggers their degradation. Together with UPF2 and UPF3, forms a surveillance complex, in which UPF2 acts as a bridge between UPF1 and UPF3. UPF2 and UPF3 are nonenzymatic components of the complex that stimulate the activity of UPF1 [ 1 ]. UPF1 has a N-terminal cysteine/histidine-rich zinc-binding domain (CH/ZBD), a regulatory 1B domain, followed by a helicase core that belongs to superfamily 1 (SF1).

This is the N-terminal CH/ZBD which contains 3 zinc binding motifs that interacts with UPF2 and it also has a cis-inhibitory effect on the ATPase activity. After binding to UPF2, the CH/ZBD suffers a large conformational change that causes the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity [ 2 , 3 ].

1. Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2. Mol Cell 41, 693-703
2. Crystal structure of the UPF2-interacting domain of nonsense-mediated mRNA decay factor UPF1. RNA 12, 1817-24
3. NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. Nat. Struct. Mol. Biol. 15, 85-93