UPF1
UPF1 (UPF1 RNA helicase and ATPase, also known as regulator of nonsense transcripts 1, RENT1, HUPF1 or smg-2) is an RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs that contain premature stop codons. It also modulates the expression level of normal mRNAs. Browse Assay Genie's current range of UPF1 research reagents below, or read on for the biology behind the target.
UPF1 is an ATP-dependent 5'-3' helicase that is active on RNA:DNA, RNA:RNA and DNA:DNA substrates carrying a 5' extension. It binds RNA, and the addition of ATP decreases RNA binding. Its ATPase activity is stimulated by single-stranded DNA, with poly(dT) and poly(dA) the most stimulatory, and is required for the disassembly of mRNPs undergoing NMD. UPF1 is recruited to mRNAs upon translation termination and goes through a cycle of phosphorylation and dephosphorylation; phosphorylation appears to be a key step in NMD.
In EJC-dependent NMD, UPF1 is recruited by release factors to stalled ribosomes together with the SMG1C kinase complex, forming the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. SURF associates with the exon junction complex through UPF2, producing a UPF1-UPF2-UPF3 surveillance complex that is believed to activate NMD. Phosphorylated UPF1 is recognised by EST1B/SMG5, SMG6 and SMG7, which link it to the mRNA degradation machinery and act as adapters for protein phosphatase 2A, triggering dephosphorylation and recycling of NMD factors. UPF1 can also activate NMD without UPF2 or UPF3, indicating alternative NMD pathways. With UPF2 and dependent on TDRD6, it mediates degradation of mRNAs with long 3'UTRs, and it contributes to replication-dependent histone mRNA degradation at the end of S phase independently of UPF2.
The UPF1 gene encodes part of a post-splicing multiprotein complex involved in mRNA nuclear export and mRNA surveillance. UniProt places the protein in the cytoplasm, P-bodies, perinuclear region and nucleus, and it belongs to the DNA2/NAM7 helicase family. The gene uses multiple polyadenylation sites, and alternative splicing yields several transcript variants. HGNC groups it with the UPF1-like RNA helicases, the SURF complex and the DECID complex. Earlier names include NORF1 and KIAA0221.
UPF1 is required for NMD, the surveillance pathway that degrades mRNAs with premature stop codons and tunes the level of normal transcripts.
UPF1 assembles into the SURF and UPF1-UPF2-UPF3 complexes, making it central to studies of how termination is coupled to mRNA decay.
Cycles of UPF1 phosphorylation by SMG1C and dephosphorylation via SMG5, SMG6, SMG7 and PP2A offer a model for regulated NMD factor turnover.
UPF1 unwinds RNA and DNA substrates 5'-3', and its ATPase activity drives mRNP disassembly, supporting mechanistic enzyme studies.
UPF1 is an RNA-dependent 5'-3' helicase and ATPase required for nonsense-mediated decay of mRNAs with premature stop codons. It is recruited at translation termination, is regulated by phosphorylation and dephosphorylation, and its ATPase activity is needed to disassemble mRNPs undergoing NMD.
UPF1 is also called regulator of nonsense transcripts 1, RENT1, HUPF1, smg-2, NORF1, pNORF1 and KIAA0221. Earlier HGNC names include UPF1 regulator of nonsense transcripts homolog (yeast). Alternative splicing gives multiple transcript variants of the UPF1 gene.
UPF1 has a mouse ortholog, Upf1, and the name smg-2 and the earlier yeast homolog designation point to conservation of the NMD factor across species. The protein belongs to the DNA2/NAM7 helicase family. Check the datasheet of any product for its validated reactivity.
Other nonsense-mediated decay factors, SURF complex components and mRNA surveillance proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q92900; product specifications from Assay Genie datasheets.