title: Staufen1-mediated mRNA decay induces Requiem mRNA decay through binding of Staufen1 to the Requiem 3'UTR.
abstract: Requiem (REQ/DPF2) was originally identified as an apoptosis-inducing protein in mouse myeloid cells and belongs to the novel Krüppel-type zinc finger d4-protein family of proteins, which includes neuro-d4 (DPF1) and cer-d4 (DPF3). Interestingly, when a portion of the REQ messenger ribonucleic acid (mRNA) 3' untranslated region (3'UTR), referred to as G8, was overexpressed in K562 cells, β-globin expression was induced, suggesting that the 3'UTR of REQ mRNA plays a physiological role. Here, we present evidence that the REQ mRNA 3'UTR, along with its trans-acting factor, Staufen1 (STAU1), is able to reduce the level of REQ mRNA via STAU1-mediated mRNA decay (SMD). By screening a complementary deoxyribonucleic acid (cDNA) expression library with an RNA-ligand binding assay, we identified STAU1 as an interactor of the REQ mRNA 3'UTR. Specifically, we provide evidence that STAU1 binds to putative 30-nucleotide stem-loop-structured RNA sequences within the G8 region, which we term the protein binding site core; this binding triggers the degradation of REQ mRNA and thus regulates translation. Furthermore, we demonstrate that siRNA-mediated silencing of either STAU1 or UPF1 increases the abundance of cellular REQ mRNA and, consequently, the REQ protein, indicating that REQ mRNA is a target of SMD.
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Graduate School for Biomedical Science and Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Jungyun
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences.
authors.forename: Jong Joo
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Ha
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences.
authors.forename: Jonghwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 380-701, Korea.
authors.forename: Chan Gil
authors.initials: CG
authors.lastname: Kim
authors.affiliation: Graduate School for Biomedical Science and Engineering, Hanyang University, Seoul 133-791, Korea jwhwang@hanyang.ac.kr.
authors.forename: Jungwook
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences cgkim@hanyang.ac.kr.
authors.forename: Chul Geun
authors.initials: CG
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D051379:Mice; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C113581:DPF2 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human; D014157:Transcription Factors