title: The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA.
abstract: Non-sense-mediated mRNA decay (NMD) is a mechanism of translation-dependent mRNA surveillance in eukaryotes: it degrades mRNAs with premature termination codons (PTCs) and contributes to cellular homeostasis by downregulating a number of physiologically important mRNAs. In the NMD pathway, Upf proteins, a set of conserved factors of which Upf1 is the central regulator, recruit decay enzymes to promote RNA cleavage. In mammals, the degradation of PTC-containing mRNAs is triggered by the exon-junction complex (EJC) through binding of its constituents Upf2 and Upf3 to Upf1. The complex formed eventually induces translational repression and recruitment of decay enzymes. Mechanisms by which physiological mRNAs are targeted by the NMD machinery in the absence of an EJC have been described but still are discussed controversially. Here, we report that the DEAD box proteins Ddx5/p68 and its paralog Ddx17/p72 also bind the Upf complex by physical interaction with Upf3, thereby interfering with the binding of EJC. By activating the NMD machinery, Ddx5 is shown to regulate the expression of its own, Ddx17 and Smg5 mRNAs. For NMD triggering, the adenosine triphosphate-binding activity of Ddx5 and the 3'-untranslated region of substrate mRNAs are essential.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Saarland, Medical Center, Building 45, 66421 Homburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Geißler
authors.forename: Simone
authors.initials: S
authors.lastname: Altmeyer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stein
authors.forename: Heike
authors.initials: H
authors.lastname: Uhlmann-Schiffler
authors.forename: Hans
authors.initials: H
authors.lastname: Stahl
mesh_terms: D020413:3' Untranslated Regions; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D059365:Nonsense Mediated mRNA Decay; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C515801:SMG5 protein, human; C435487:UPF3A protein, human; C435488:UPF3B protein, human; C026452:messenger ribonucleoprotein; C102004:DDX17 protein, human; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases