title: AUF1 promotes let-7b loading on Argonaute 2.
abstract: Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (Kd = ∼ 6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2-let-7 triggered target mRNA decay. Our findings uncover a novel mechanism by which AUF1 binding and transfer of microRNA let-7 to AGO2 facilitates let-7-elicited gene silencing.
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Physics and Astronomy, Institute of Applied Physics, National Center for Creative Research Initiatives, Seoul National University, Seoul 151-747, Korea;
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Jo
authors.affiliation: Department of Biochemistry and Molecular Biology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors.forename: Elizabeth J F
authors.initials: EJ
authors.lastname: White
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Supriyo
authors.initials: S
authors.lastname: De
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases-Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Markus
authors.initials: M
authors.lastname: Hafner
authors.affiliation: Department of Biochemistry and Molecular Biology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors.forename: Beth E
authors.initials: BE
authors.lastname: Zucconi
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.affiliation: Cancer Metastasis Control Center, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-338, Korea;
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Shin
authors.affiliation: Cancer Metastasis Control Center, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-338, Korea;
authors.forename: Ji-Joon
authors.initials: JJ
authors.lastname: Song
authors.affiliation: Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Department of Biochemistry and Molecular Biology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Wilson
authors.affiliation: Department of Physics and Astronomy, Institute of Applied Physics, National Center for Creative Research Initiatives, Seoul National University, Seoul 151-747, Korea;
authors.forename: Sungchul
authors.initials: S
authors.lastname: Hohng
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D020868:Gene Silencing / Q000502:physiology*; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D011485:Protein Binding; D020871:RNA Stability / Q000502:physiology
chemical_list: D060565:Argonaute Proteins; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Argonaute; RISC; hnRNP D; microRNA; ribonucleoprotein complex