title: Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
abstract: Mammalian Staufen (Stau)1 is an RNA binding protein that is thought to function in mRNA transport and translational control. Nonsense-mediated mRNA decay (NMD) degrades abnormal and natural mRNAs that terminate translation sufficiently upstream of a splicing-generated exon-exon junction. Here we describe an mRNA decay mechanism that involves Stau1, the NMD factor Upf1, and a termination codon. Unlike NMD, this mechanism does not involve pre-mRNA splicing and occurs when Upf2 or Upf3X is downregulated. Stau1 binds directly to Upf1 and elicits mRNA decay when tethered downstream of a termination codon. Stau1 also interacts with the 3'-untranslated region of ADP-ribosylation factor (Arf)1 mRNA. Accordingly, downregulating either Stau1 or Upf1 increases Arf1 mRNA stability. These findings suggest that Arf1 mRNA is a natural target for Stau1-mediated decay, and data indicate that other mRNAs are also natural targets. We discuss this pathway as a means for cells to downregulate the expression of Stau1 binding transcripts.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
authors.forename: Luc
authors.initials: L
authors.lastname: Furic
authors.forename: Luc
authors.initials: L
authors.lastname: Desgroseillers
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Maquat
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D018388:Codon, Terminator / Q000235:genetics; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D020365:RNA Helicases; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D020413:3' Untranslated Regions; D018388:Codon, Terminator; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C492187:Stau1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human; D020823:ADP-Ribosylation Factor 1