title: Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.
abstract: RNA quality-control pathways get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the adenosine triphosphatase (ATPase) cycle of the SF1 helicase Upf1 is required for mRNA discrimination during nonsense-mediated decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD-translation and termination codon-proximal poly(A) binding protein-depend on the ATPase activity of Upf1 to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be a widely used activity in target RNA discrimination.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Pratt
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Physiology, National University of Singapore, Singapore 119077, Singapore; Molecular Engineering Laboratory, A(∗)STAR, Singapore 138632, Singapore. Electronic address: geneyeo@ucsd.edu.
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jlykkeandersen@ucsd.edu.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykke-Andersen
mesh_terms: D020413:3' Untranslated Regions; D000255:Adenosine Triphosphate / Q000378:metabolism*; D020134:Catalytic Domain; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay; D020365:RNA Helicases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D015534:Trans-Activators; D000255:Adenosine Triphosphate; D020365:RNA Helicases; C101828:UPF1 protein, human