| Structural highlights
2xzo is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 2wjv, 2wjy, 2iyk, 2xzp, 2gjk, 2gk7, 2gk6 |
| Activity: | RNA helicase, with EC number 3.6.4.13 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RENT1_HUMAN] RNA-dependent helicase and ATPase required for nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. 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. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. 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. 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. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. 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. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Upf1 is a crucial factor in nonsense-mediated mRNA decay, the eukaryotic surveillance pathway that degrades mRNAs containing premature stop codons. The essential RNA-dependent ATPase activity of Upf1 is triggered by the formation of the surveillance complex with Upf2-Upf3. We report crystal structures of Upf1 in the presence and absence of the CH domain, captured in the transition state with ADP:AlF(4)(-) and RNA. In isolation, Upf1 clamps onto the RNA, enclosing it in a channel formed by both the catalytic and regulatory domains. Upon binding to Upf2, the regulatory CH domain of Upf1 undergoes a large conformational change, causing the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity. Formation of the surveillance complex thus modifies the RNA binding properties and the catalytic activity of Upf1, causing it to switch from an RNA-clamping mode to an RNA-unwinding mode.
Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2.,Chakrabarti S, Jayachandran U, Bonneau F, Fiorini F, Basquin C, Domcke S, Le Hir H, Conti E Mol Cell. 2011 Mar 18;41(6):693-703. PMID:21419344[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lykke-Andersen J, Shu MD, Steitz JA. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000 Dec 22;103(7):1121-31. PMID:11163187
- ↑ Kaygun H, Marzluff WF. Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1. Nat Struct Mol Biol. 2005 Sep;12(9):794-800. Epub 2005 Aug 7. PMID:16086026 doi:http://dx.doi.org/10.1038/nsmb972
- ↑ Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708. PMID:18172165 doi:10.1101/gad.1622708
- ↑ Franks TM, Singh G, Lykke-Andersen J. Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay. Cell. 2010 Dec 10;143(6):938-50. doi: 10.1016/j.cell.2010.11.043. PMID:21145460 doi:http://dx.doi.org/10.1016/j.cell.2010.11.043
- ↑ Chakrabarti S, Jayachandran U, Bonneau F, Fiorini F, Basquin C, Domcke S, Le Hir H, Conti E. Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2. Mol Cell. 2011 Mar 18;41(6):693-703. PMID:21419344 doi:10.1016/j.molcel.2011.02.010
- ↑ Chakrabarti S, Jayachandran U, Bonneau F, Fiorini F, Basquin C, Domcke S, Le Hir H, Conti E. Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2. Mol Cell. 2011 Mar 18;41(6):693-703. PMID:21419344 doi:10.1016/j.molcel.2011.02.010
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