title: Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the alpha-globin mRNA stability complex.
abstract: mRNA turnover is an important regulatory component of gene expression and is significantly influenced by ribonucleoprotein (RNP) complexes which form on the mRNA. Studies of human alpha-globin mRNA stability have identified a specific RNP complex (alpha-complex) which forms on the 3' untranslated region (3'UTR) of the mRNA and appears to regulate the erythrocyte-specific accumulation of alpha-globin mRNA. One of the protein activities in this multiprotein complex is a poly(C)-binding activity which consists of two proteins, alphaCP1 and alphaCP2. Neither of these proteins, individually or as a pair, can bind the alpha-globin 3'UTR unless they are complexed with the remaining non-poly(C) binding proteins of the alpha-complex. With the yeast two-hybrid screen, a second alpha-complex protein was identified. This protein is a member of the previously identified A+U-rich (ARE) binding/degradation factor (AUF1) family of proteins, which are also known as the heterogeneous nuclear RNP (hnRNP) D proteins. We refer to these proteins as AUF1/hnRNP-D. Thus, a protein implicated in ARE-mediated mRNA decay is also an integral component of the mRNA stabilizing alpha-complex. The interaction of AUF1/hnRNP-D is more efficient with alphaCP1 relative to alphaCP2 both in vitro and in vivo, suggesting that the alpha-complex might be dynamic rather than a fixed complex. AUF1/hnRNP-D could, therefore, be a general mRNA turnover factor involved in both stabilization and decay of mRNA.
authors.affiliation: Department of Cell, Developmental and Neurobiology, Rutgers University, Piscataway, New Jersey 08855, USA. kiledjia@biology.rutgers.edu
authors.forename: M
authors.initials: M
authors.lastname: Kiledjian
authors.forename: C T
authors.initials: CT
authors.lastname: DeMaria
authors.forename: G
authors.initials: G
authors.lastname: Brewer
authors.forename: K
authors.initials: K
authors.lastname: Novick
mesh_terms: D004268:DNA-Binding Proteins; D005914:Globins / Q000235:genetics*; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D011066:Poly C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; C094604:PCBP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011066:Poly C; D005914:Globins