# UPF1 (Q92900) research notes

## Summary
UPF1 (regulator of nonsense transcripts 1; RENT1) is the central ATP-dependent RNA helicase and ATPase of the nonsense-mediated mRNA decay (NMD) pathway. A superfamily-1 (SF1) helicase with an N-terminal cysteine-histidine-rich (CH) zinc-binding regulatory domain, UPF1 is recruited to mRNAs at translation termination, where release factors (eRF1/eRF3) and the SMG1 kinase complex assemble the transient SURF complex. In EJC-dependent NMD the adaptor UPF2 bridges UPF1 to UPF3 and the downstream exon-junction complex, forming the UPF1-UPF2-UPF3 surveillance complex; UPF1 is then phosphorylated by SMG1 and the phospho-form is recognized by SMG5/SMG6/SMG7 to recruit decay enzymes and PP2A. UPF1 ATPase/helicase activity remodels and disassembles target mRNPs, committing premature-termination-codon-containing and certain long-3'UTR or staufen-bound transcripts to degradation, and also mediates replication-dependent histone mRNA decay at the end of S phase. UPF1 acts mainly on cytoplasmic translating mRNAs (with a smaller nuclear pool), concentrates in P-bodies in its hyperphosphorylated state, and has additional reported moonlighting roles at telomeres and in DNA replication; it can unwind both RNA and DNA in vitro.

## Core functions (from review)
- **GO:0003724 RNA helicase activity** — ATP-dependent RNA helicase / ATPase that, recruited at translation termination, remodels and disassembles target mRNPs to drive nonsense-mediated mRNA decay.
- **GO:0003724 RNA helicase activity** — Central effector of nonsense-mediated mRNA decay of premature-termination-codon-containing transcripts; recruited at terminating ribosomes and, via SMG1 phosphorylation and the UPF2/UPF3-EJC surveillance complex, commits target mRNAs to degradation.

## Provenance
Research and verbatim supporting quotes are recorded inline in `UPF1-ai-review.yaml` (per-annotation `supported_by` and `references` findings). This notes file summarizes the completed review; see the YAML for evidence citations.