title: Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability.
abstract: Although tumor protein D52 (TPD52) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation (RIP) assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than are TPD53 and TPD54. We subsequently focused on the 3'-untranslated region (3'-UTR) of TPD52 as acis-acting element in post-transcriptional gene regulation. Several deletion mutants of the 3'-UTR of TPD52 mRNA were constructed and ligated to the 3'-end of a reporter green fluorescence protein gene. An RNA degradation assay revealed that a minimalcis-acting region, located in the 78-280 region of the 5'-proximal region of the 3'-UTR, stabilized the reporter mRNA. Biotin pull-down and RIP assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3'-end of the 78-280 fragment. Stimulation of transforming growth factor-β and epidermal growth factor decreased the binding ability of these factors, resulting in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as acis-acting element andtrans-acting factor(s), respectively. Thus, we here report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan mukudai@dent.showa-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mukudai
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Shimane
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.|Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shirota
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D047468:Immunoprecipitation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements; D017384:Sequence Deletion; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D020413:3' Untranslated Regions; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C114751:TPD52 protein, human; C486416:TPD52L1 protein, human; C486414:TPD52L2 protein, human; C076751:TIAL1 protein, human
keywords: RNA-binding proteins; TIA-1; TIAR; TPD52; mRNA stability; post-transcriptional regulation