title: lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements.
abstract: Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) involves the degradation of translationally active mRNAs whose 3'-untranslated regions (3' UTRs) bind to STAU1, a protein that binds to double-stranded RNA. Earlier studies defined the STAU1-binding site within ADP-ribosylation factor 1 (ARF1) mRNA as a 19-base-pair stem with a 100-nucleotide apex. However, we were unable to identify comparable structures in the 3' UTRs of other targets of SMD. Here we show that STAU1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3' UTR of an SMD target and another Alu element in a cytoplasmic, polyadenylated long non-coding RNA (lncRNA). An individual lncRNA can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions of non-coding RNAs and Alu elements. Not all mRNAs that contain an Alu element in the 3' UTR are targeted for SMD even in the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known trans-acting RNA effectors consist of fewer than 200 nucleotides, and these include small nucleolar RNAs and microRNAs. Our finding that the binding of STAU1 to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNAs. We name these lncRNAs half-STAU1-binding site RNAs (1/2-sbsRNAs).
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Gong
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Maquat
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020087:Alu Elements / Q000235:genetics*; D020029:Base Pairing; D001665:Binding Sites; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D009690:Nucleic Acid Conformation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011061:Poly A / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D020365:RNA Helicases; D020871:RNA Stability; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012984:Software; D013379:Substrate Specificity; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; D017395:Plasminogen Activator Inhibitor 1; D011506:Proteins; D012330:RNA, Double-Stranded; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; C051321:SERPINE1 protein, human; C556125:SOWAHC protein, human; C492185:STAU1 protein, human; D015534:Trans-Activators; D011061:Poly A; D020365:RNA Helicases; C101828:UPF1 protein, human