title: MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs.
abstract: RNA helicases are important regulators of gene expression that act by remodeling RNA secondary structures and RNA-protein interactions. Here, we demonstrate that MOV10 has an ATP-dependent 5' to 3' in vitro RNA unwinding activity and determine the RNA-binding sites of MOV10 and its helicase mutants using PAR-CLIP. We find that MOV10 predominantly binds to 3' UTRs upstream of regions predicted to form local secondary structures and provide evidence that MOV10 helicase mutants are impaired in their ability to translocate 5' to 3' on their mRNA targets. MOV10 interacts with UPF1, the key component of the nonsense-mediated mRNA decay pathway. PAR-CLIP of UPF1 reveals that MOV10 and UPF1 bind to RNA in close proximity. Knockdown of MOV10 resulted in increased mRNA half-lives of MOV10-bound as well as UPF1-regulated transcripts, suggesting that MOV10 functions in UPF1-mediated mRNA degradation as an RNA clearance factor to resolve structures and displace proteins from 3' UTRs.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Lea H
authors.initials: LH
authors.lastname: Gregersen
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schueler
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Munschauer
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Mastrobuoni
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kempa
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Dieterich
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany. Electronic address: markus.landthaler@mdc-berlin.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Landthaler
mesh_terms: D020413:3' Untranslated Regions; D020816:Amino Acid Motifs; D001665:Binding Sites; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay; D021381:Protein Transport; D020365:RNA Helicases / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C530476:Mov10 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human