title: Identification of TIAR as a protein binding to the translational regulatory AU-rich element of tumor necrosis factor alpha mRNA.
abstract: In monocyte/macrophages, the translation of tumor necrosis factor alpha (TNF-alpha) mRNA is tightly regulated. In unstimulated cells, translation of TNF-alpha mRNA is blocked. Upon stimulation with lipopolysaccharides, this repression is overcome, and the mRNA becomes efficiently translated. The key element in this regulation is the AU-rich element (ARE). We have previously reported the binding of two cytosolic protein complexes to the TNF-alpha mRNA ARE. One of these complexes (complex 1) forms with extracts of both unstimulated and lipopolysaccharide-stimulated macrophages and requires a large fragment of the ARE containing clustered AUUUA pentamers. The other complex (complex 2) is only detected after cell activation, binds to a minimal UUAUUUAUU nonamer, and is composed of a 55-kDa protein. Here, we report the identification of the RNA-binding protein TIAR as a protein involved in complex 1. The RNA sequence bound by TIAR and the cytoplasmic localization of this protein in macrophages argue for an involvement of TIAR in TNF mRNA posttranscriptional regulation.
authors.affiliation: Laboratoire de Chimie Biologique, Université Libre de Bruxelles, 67 rue des chevaux, 1640 Rhode Saint Genèse, Belgium. cgueydan@alize.ulb.ac.be
authors.forename: C
authors.initials: C
authors.lastname: Gueydan
authors.forename: L
authors.initials: L
authors.lastname: Droogmans
authors.forename: P
authors.initials: P
authors.lastname: Chalon
authors.forename: G
authors.initials: G
authors.lastname: Huez
authors.forename: D
authors.initials: D
authors.lastname: Caput
authors.forename: V
authors.initials: V
authors.lastname: Kruys
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C489665:Tial1 protein, mouse; D014409:Tumor Necrosis Factor-alpha