The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3 - PubMed (original) (raw)
doi: 10.1038/nsmb741. Epub 2004 Mar 7.
Affiliations
- PMID: 15004547
- DOI: 10.1038/nsmb741
The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3
Jan Kadlec et al. Nat Struct Mol Biol. 2004 Apr.
Abstract
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which eukaryotic cells detect and degrade transcripts containing premature termination codons. Three 'up-frameshift' proteins, UPF1, UPF2 and UPF3, are essential for this process in organisms ranging from yeast to human. We present a crystal structure at a resolution of 1.95 A of the complex between the interacting domains of human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-binding domain). The protein-protein interface is mediated by highly conserved charged residues in UPF2 and UPF3b and involves the beta-sheet surface of the UPF3b RNP domain, which is generally used by these domains to bind nucleic acids. We show that the UPF3b RNP does not bind RNA, whereas the UPF2 construct and the complex do. Our results advance understanding of the molecular mechanisms underlying the NMD quality control process.
Comment in
- Making structural sense of nonsense-mediated decay.
Lykke-Andersen J. Lykke-Andersen J. Nat Struct Mol Biol. 2004 Apr;11(4):305-6. doi: 10.1038/nsmb0404-305. Nat Struct Mol Biol. 2004. PMID: 15048104 No abstract available.
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