title: The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells.
abstract: MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors. Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.
authors.affiliation: Faculty of Science, University of Technology, Sydney, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: Connerty
authors.affiliation: Faculty of Engineering and Information Technology, Centre of Health Technologies, University of Technology, Sydney, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bajan
authors.affiliation: Division of Cancer Research, Jacqui Wood Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Judit
authors.initials: J
authors.lastname: Remenyi
authors.affiliation: Division of Cancer Research, Jacqui Wood Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Frances V
authors.initials: FV
authors.lastname: Fuller-Pace
authors.affiliation: Faculty of Engineering and Information Technology, Centre of Health Technologies, University of Technology, Sydney, Australia. Electronic address: gyorgy.hutvagner@uts.edu.au.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Hutvagner
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C105789:KHSRP protein, human; C549214:MIRN19A microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D015534:Trans-Activators; C487931:mirnlet7 microRNA, human; D008156:Luciferases; C102004:DDX17 protein, human; D053487:DEAD-box RNA Helicases
keywords: Argonaute; DDX17; KHSRP; miRNA; p72