Regulator of nonsense transcripts 1 (UPF1) (UPF1)

Regulator of nonsense transcripts 1 (UPF1) is a highly conserved ATP-dependent RNA helicase that serves as the central engine of the nonsense-mediated mRNA decay (NMD) pathway (UniProt, PMC2991074). It functions as a molecular surveillance factor, identifying and targeting mRNAs with premature termination codons (PTCs) for rapid degradation to prevent the synthesis of truncated, potentially toxic proteins (NCBI Gene, PMC1782376). Beyond its primary role in NMD, UPF1 is involved in various other RNA decay pathways, DNA replication, and telomere maintenance, making it a critical regulator of cellular homeostasis (PMC2663315, Wikipedia). In disease contexts, UPF1 is often dysregulated; its downregulation is linked to several cancers where it acts as a tumor suppressor, while its modulation is being explored as a therapeutic strategy for genetic diseases caused by nonsense mutations (PMC9858311, Creative Biolabs). Pharmacological targeting of UPF1, primarily through small-molecule inhibitors that disrupt its interactions with other NMD factors like SMG5 or SMG7, aims to stabilize beneficial transcripts or enhance the efficacy of read-through therapies (AACR, PMC3518452). However, its essential role in development and genome stability presents significant challenges for therapeutic window and safety (PMC3603218, PMC2663315).

Other names

UPF1RENT1HUPF1SMG2NORF1ATP-dependent helicase RENT1Nonsense mRNA reducing factor 1Up-frameshift suppressor 1 homolog

Inhibition of nonsense-mediated mRNA decay (NMD) by disrupting UPF1 interactions with SMG proteins or inhibiting its ATPase/helicase activity (Santa Cruz Biotech, AACR, PMC3518452).