title: Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities.
abstract: RNA helicases are implicated in most cellular RNA-dependent events. In eukaryotes however, only few have been functionally characterized. Upf1 is a RNA helicase essential for nonsense-mediated mRNA decay (NMD). Here, using magnetic tweezers and bulk assays, we observe that human Upf1 is able to translocate slowly over long single-stranded nucleic acids with a processivity >10 kb. Upf1 efficiently translocates through double-stranded structures and protein-bound sequences, demonstrating that Upf1 is an efficient ribonucleoprotein complex remodeler. Our observation of processive unwinding by an eukaryotic RNA helicase reveals that Upf1, once recruited onto NMD mRNA targets, can scan the entire transcript to irreversibly remodel the mRNP, facilitating its degradation by the NMD machinery.
authors.affiliation: 1] Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, Paris 75230, France [2] Institut de Biologie de l'Ecole Normale Supérieure, INSERM U1024, Paris 75230, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fiorini
authors.affiliation: 1] Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, Paris 75230, France [2] Institut de Biologie de l'Ecole Normale Supérieure, INSERM U1024, Paris 75230, France [3] Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie Paris, Université Paris Diderot, CNRS, 24 rue Lhomond, Paris 75005, France.
authors.forename: Debjani
authors.initials: D
authors.lastname: Bagchi
authors.affiliation: 1] Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, Paris 75230, France [2] Institut de Biologie de l'Ecole Normale Supérieure, INSERM U1024, Paris 75230, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Hir
authors.affiliation: 1] Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, Paris 75230, France [2] Institut de Biologie de l'Ecole Normale Supérieure, INSERM U1024, Paris 75230, France [3] Laboratoire de Physique Statistique, Ecole Normale Supérieure, Université Pierre et Marie Curie Paris, Université Paris Diderot, CNRS, 24 rue Lhomond, Paris 75005, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Croquette
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004926:Escherichia coli; D018014:Gene Transfer Techniques; D006801:Humans; D066298:In Vitro Techniques; D059365:Nonsense Mediated mRNA Decay; D020365:RNA Helicases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D015534:Trans-Activators; C026452:messenger ribonucleoprotein; D004247:DNA; D020365:RNA Helicases; C101828:UPF1 protein, human