title: The cryo-EM structure of the UPF-EJC complex shows UPF1 poised toward the RNA 3' end.
abstract: Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance pathway that degrades aberrant mRNAs containing premature termination codons (PTCs). NMD is triggered upon the assembly of the UPF surveillance complex near a PTC. In humans, UPF assembly is prompted by the exon junction complex (EJC). We investigated the molecular architecture of the human UPF complex bound to the EJC by cryo-EM and using positional restraints from additional EM, MS and biochemical interaction data. The heptameric assembly is built around UPF2, a scaffold protein with a ring structure that closes around the CH domain of UPF1, keeping the helicase region in an accessible and unwinding-competent state. UPF2 also positions UPF3 to interact with the EJC. The geometry is such that this transient complex poises UPF1 to elicit helicase activity toward the 3' end of the mRNP.
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (Spanish National Research Council), Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Melero
authors.forename: Gretel
authors.initials: G
authors.lastname: Buchwald
authors.forename: Raquel
authors.initials: R
authors.lastname: Castaño
authors.forename: Monika
authors.initials: M
authors.lastname: Raabe
authors.forename: David
authors.initials: D
authors.lastname: Gil
authors.forename: Melisa
authors.initials: M
authors.lastname: Lázaro
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
authors.forename: Oscar
authors.initials: O
authors.lastname: Llorca
mesh_terms: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D020285:Cryoelectron Microscopy / Q000379:methods; D005091:Exons; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D020365:RNA Helicases / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; C435487:UPF3A protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human