UPF1 RNA helicase and ATPase (UPF1)

UPF1 RNA helicase and ATPase (UPF1) is a highly conserved, multifunctional protein that serves as the master regulator of the nonsense-mediated mRNA decay (NMD) pathway (UniProt P78347). It functions as an ATP-dependent RNA helicase that translocates along RNA to displace proteins and remodel ribonucleoprotein complexes, a process essential for the surveillance and degradation of transcripts containing premature termination codons (PubMed: 28223409). Beyond its primary role in NMD, UPF1 is involved in telomere maintenance, DNA replication stress responses, and the regulation of various RNA decay pathways (NCBI Gene: 5976). In the context of human disease, UPF1 is a target of interest in oncology, where NMD inhibition can enhance the expression of tumor-specific neoantigens, potentially sensitizing tumors to immunotherapy (PubMed: 31533975). Additionally, UPF1 modulation is explored in genetic disorders caused by nonsense mutations, where suppressing NMD may restore the expression of truncated but functional proteins (PubMed: 24532341). In neurodegenerative conditions like Amyotrophic Lateral Sclerosis (ALS), UPF1 has shown neuroprotective effects by clearing toxic RNA species (PubMed: 26300005). While no UPF1-targeted therapies are currently FDA-approved, small molecule inhibitors like NMDI-1 and antisense oligonucleotides are being utilized in preclinical research to evaluate the therapeutic potential of NMD modulation (PubChem CID: 2826652).

Other names

RENT1HUPF1NORF1Regulator of nonsense transcripts 1ATP-dependent RNA helicase UPF1

Inhibition of the nonsense-mediated mRNA decay (NMD) pathway by blocking UPF1 phosphorylation or its helicase activity.