Regulator of nonsense transcripts 2 (UPF2) (UPF2)

Regulator of nonsense transcripts 2 (UPF2) is a core protein component of the nonsense-mediated mRNA decay (NMD) pathway, a vital cellular surveillance mechanism that detects and degrades mRNAs containing premature termination codons (PTCs) [1, 2]. UPF2 acts as a critical adapter, bridging the interaction between the exon junction complex-associated protein UPF3 and the central NMD helicase UPF1, which is necessary for the activation of the decay process [5]. From a therapeutic perspective, UPF2 is a target of interest for treating genetic disorders caused by nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy, where NMD inhibition can stabilize the transcript and restore protein function [4]. Additionally, UPF2 is a potential target in cancer immunotherapy, as NMD often degrades transcripts encoding tumor-specific neoantigens; inhibiting UPF2 could thus enhance the immune system's ability to recognize and attack cancer cells [4]. However, because NMD also regulates the expression of many normal physiological transcripts, systemic inhibition of UPF2 poses significant safety challenges, including potential developmental toxicity and neurodevelopmental risks, as evidenced by the association of UPF2 mutations with X-linked intellectual disability [3].

Other names

UPF2RENT2HUPF2Nonsense mRNA reducing factor 2smg-3

Inhibition of the nonsense-mediated mRNA decay (NMD) pathway to stabilize transcripts with premature termination codons [4]