Regulator of nonsense transcripts 2 (UPF2)

Regulator of nonsense transcripts 2 (UPF2) is a highly conserved RNA-binding protein and core component of the nonsense-mediated mRNA decay (NMD) pathway, a critical post-transcriptional quality control mechanism in eukaryotic cells. UPF2 acts as a scaffold, facilitating interactions between other NMD factors (notably UPF1 and UPF3b) and the exon junction complex, and is essential for detecting and degrading mRNAs with premature termination codons, thereby preventing the translation of potentially deleterious truncated proteins. The NMD pathway, orchestrated by UPF2, influences overall transcriptome fidelity, regulates alternative splicing, and gene expression, and is crucial during organ development, including in the liver and testes. Loss of UPF2 function leads to impaired cell cycle progression, defective tissue regeneration (e.g., failure of liver regeneration after injury), and, in the testis, results in severe atrophy and male infertility due to the accumulation of aberrant mRNAs and loss of Sertoli and germ cells. UPF2 itself is not currently known to be directly targeted by therapeutic drugs, nor is there substantial evidence associating UPF2 as a biomarker or safety concern in the clinical setting.

Other names

UPF2KIAA1408RENT2hUpf2DKFZP434D222smg-3Up-frameshift suppressor 2 homolognonsense mediated mRNA decay factorHUPF2FRS2/UPF2/LEMD3 fusionLEMD3/UPF2 fusionyeast Upf2p homolog