Up-frameshift protein 1 (UPF1)

Up-frameshift protein 1 (UPF1) is a highly conserved ATP-dependent RNA helicase and ATPase that plays a central role in the nonsense-mediated mRNA decay (NMD) pathway, a fundamental mRNA surveillance mechanism that degrades messenger RNAs containing premature stop codons and regulates the abundance of many normal mRNAs[2][4]. UPF1 operates as a monomeric helicase with high processivity on nucleic acids; it translocates along and unwinds RNA secondary structures using energy from ATP hydrolysis[1][2][3][4]. The protein has a structurally unique helicase core with two RecA-like domains and subdomains critical for RNA binding and regulation[1][2]. UPF1 function is dynamically regulated—its ATPase activity is autoinhibited until activated by interacting proteins such as UPF2, which is essential for efficient NMD[3]. Mutations in UPF1 can disrupt NMD and are implicated in several human diseases, particularly cancer and neurodegeneration[2][3][4]. While there are no approved drugs directly targeting UPF1, its pivotal role in RNA surveillance makes it an attractive candidate for future therapeutic modulation, albeit with significant safety considerations due to the essential nature of NMD in cell homeostasis.

Other names

Regulator of nonsense transcripts 1RENT1SMG2

Molecules (not yet specific drugs) targeting UPF1 could modulate NMD through inhibition or activation of its helicase or ATPase activity, affecting mRNA decay.