UPF1

This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located only in the cytoplasm. When translation ends, it interacts with the protein that is a functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

UPF1, RNA Helicase And ATPase

RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs (PubMed:11163187, PubMed:16086026, PubMed:18172165, PubMed:21145460, PubMed:21419344, PubMed:24726324).
Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD (PubMed:11544179, PubMed:25220460).
Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104).
In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD (PubMed:21419344).
Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors (PubMed:12554878).
UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (PubMed:18447585).
Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (PubMed:16086026, PubMed:18172165).
For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585, PubMed:25220460).
The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (PubMed:21145460).
Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (By similarity).
Also capable of unwinding double-stranded DNA and translocating on single-stranded DNA (PubMed:30218034).

Biological Process 3'-UTR-mediated mRNA destabilization Source:UniProtKB1 Publication
Biological Process cell cycle phase transition Source:UniProtKB1 Publication
Biological Process cellular response to interleukin-1 Source:UniProtKB1 Publication
Biological Process cellular response to lipopolysaccharide Source:UniProtKB1 Publication
Biological Process DNA duplex unwinding Source:UniProtKB1 Publication
Biological Process DNA repair Source:HGNC-UCL1 Publication
Biological Process DNA replication Source:HGNC-UCL1 Publication
Biological Process histone mRNA catabolic process Source:UniProtKB1 Publication
Biological Process mRNA export from nucleus Source:HGNC-UCL1 Publication
Biological Process nuclear-transcribed mRNA catabolic process Source:UniProtKB1 Publication
Biological Process nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay Source:UniProtKB1 Publication
Biological Process nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Source:UniProtKB1 Publication
Biological Process positive regulation of mRNA catabolic process Source:UniProtKB1 Publication
Biological Process regulation of telomere maintenance Source:BHF-UCL1 Publication
Biological Process regulation of translational termination Source:UniProtKB1 Publication
Biological Process telomere maintenance via semi-conservative replication Source:BHF-UCL1 Publication

Cytoplasm
Cytoplasm, P-body
Nucleus
Cytoplasm, perinuclear region
Hyperphosphorylated form is targeted to the P-body, while unphosphorylated protein is distributed throughout the cytoplasm. Localized in the chromatoid bodies of round spermatids (By similarity).

Phosphorylated by SMG1; required for formation of mRNA surveillance complexes.