# UPF3A (Q9H1J1) research notes

## Summary
UPF3A (Regulator of nonsense transcripts 3A; hUpf3p/hUPF3L) is a nonsense-mediated mRNA decay (NMD) factor and the paralog of UPF3B. It is a nuclear/cytoplasmic shuttling protein that associates with the exon-junction complex (EJC) deposited upstream of exon-exon junctions on spliced mRNA and acts as a molecular adaptor bridging the EJC to the core NMD machinery, binding UPF2 (and RBM8A/EJC) and helping assemble the UPF1-UPF2-UPF3 surveillance complex that licenses decay of premature-termination-codon-containing mRNAs. UPF3A is only marginally active in promoting NMD compared with UPF3B; because the two paralogs compete for the same MIF4G-III surface of UPF2, UPF3A can act as an NMD antagonist/repressor by sequestering UPF2, and in many tissues UPF3A is itself cleared but is stabilized by binding UPF2 when functional UPF3B is absent. UPF3A also binds spliced mRNA and weakly stimulates translation in vitro, and has been reported to bind telomeric-repeat (TERRA) RNA/DNA in the context of telomere RNA surveillance. Through these activities UPF3A contributes to the magnitude and substrate selectivity of NMD and to paralog-buffering of the NMD pathway during development.

## Core functions (from review)
- **GO:0003729 mRNA binding** — Nonsense-mediated mRNA decay (NMD) adaptor that associates with the exon-junction complex on spliced mRNA and bridges it to the core NMD machinery, binding UPF2 (and RBM8A/EJC) and helping assemble the UPF1-UPF2-UPF3 surveillance complex that targets premature-termination-codon-containing mRNAs.
- **GO:0140311 protein sequestering activity** — NMD modulator/antagonist; UPF3A is only marginally active in promoting decay and competes with UPF3B for UPF2, sequestering UPF2 to repress/buffer NMD, contributing to paralog-dependent control of NMD magnitude.

## Provenance
Research and verbatim supporting quotes are recorded inline in `UPF3A-ai-review.yaml` (per-annotation `supported_by` and `references` findings). This notes file summarizes the completed review; see the YAML for evidence citations.