title: Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells.
abstract: The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3'untranslated region (3'UTR) contains a highly conserved AU-rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU-rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR-mediated activation. Mutational and RNA-interference evidence also supports an AUF1 (AU-factor-1, HNRNPD, HGNC:5036) contribution to the observed repressive activity of the 3'UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE-binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site.
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Fotinos
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey.
authors.forename: David T
authors.initials: DT
authors.lastname: Fritz
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey.
authors.forename: Steven
authors.initials: S
authors.lastname: Lisica
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey.
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Rogers
mesh_terms: D020413:3' Untranslated Regions; D063307:AU Rich Elements; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D000067780:ELAV-Like Protein 1 / Q000378:metabolism; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D000067780:ELAV-Like Protein 1; C000593997:Elavl1 protein, mouse; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D035683:MicroRNAs
keywords: GENE REGULATION; GROWTH FACTOR; MESENCHYMAL CELL; POST-TRANSCRIPTIONAL