Upf1, also known as Up-frameshift protein 1, is a vital controller for transcripts. It is a key element in mRNA decay pathways, especially in nonsense-mediated mRNA decay (NMD), where it specifically degrades premature termination codon (PTC)-containing products. Additionally, it may act as an E3 ligase to degrade target proteins independently of mRNA decay, protecting cells from misfolded polypeptides. NMD and other UPF1-mediated RNA decay pathways are crucial for maintaining cellular homeostasis and gene expression regulation [1,3,6].

In cancer, UPF1 is often downregulated, and its low expression is correlated with poor prognosis. Dysfunction of UPF1 leads to the failure of NMD, contributing to tumor initiation and progression, suggesting it could be a potential biomarker for cancer diagnosis and treatment [2,7]. In terms of RNA regulation, Upf1 binds to poorly translated and untranslated open reading frames (ORFs), regulating mRNA stability through an exon-junction complex (EJC)-independent nonsense-mediated decay pathway called ORF-mediated decay (OMD) [5]. Also, it is involved in structure-mediated RNA decay along with G3BP1, and viral RNAs are susceptible to Upf1-mediated RNA decay pathways, though viruses have evolved ways to escape [4,8].

In conclusion, Upf1 is essential for mRNA surveillance and protein quality control. Its role in NMD and other decay pathways is crucial for cellular function. The study of Upf1 in cancer through various models has revealed its potential as a biomarker, and its functions in mRNA stability regulation and viral RNA targeting highlight its broad biological significance.