title: Ge-1 is a central component of the mammalian cytoplasmic mRNA processing body.
abstract: The mRNA processing body (P-body) is a cellular structure that regulates gene expression by degrading cytoplasmic mRNA. The objective of this study was to identify and characterize novel components of the mammalian P-body. Approximately 5% of patients with the autoimmune disease primary biliary cirrhosis have antibodies directed against this structure. Serum from one of these patients was used to identify a cDNA encoding Ge-1, a 1,401-amino-acid protein. Ge-1 contains an N-terminal WD 40 motif and C-terminal domains characterized by a repeating psi(X(2-3)) motif. Ge-1 co-localized with previously identified P-body components, including proteins involved in mRNA decapping (DCP1a and DCP2) and the autoantigen GW 182. The Ge-1 C-terminal domain was necessary and sufficient to target the protein to P-bodies. Following exposure of cells to oxidative stress, Ge-1-containing P-bodies were found adjacent to TIA-containing stress granules. During the recovery period, TIA returned to the nucleus while Ge-1-containing P-bodies localized to the perinuclear region. siRNA-mediated knock-down of Ge-1 resulted in loss of P-bodies containing Ge-1, DCP1a, and DCP2. In contrast, Ge-1-containing P-bodies persisted despite knock-down of DCP2. Taken together, the results of this study show that Ge-1 is a central component of P-bodies and suggest that Ge-1 may act prior to the 5(')-decapping step in mRNA degradation.
authors.affiliation: Department of Medicine, Havard Medical School, the Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Charlestown, MA 02129, USA.
authors.forename: Jiang Hong
authors.initials: JH
authors.lastname: Yu
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Yang
authors.forename: Tod
authors.initials: T
authors.lastname: Gulick
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Donald B
authors.initials: DB
authors.lastname: Bloch
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000906:Antibodies / Q000378:metabolism; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D022083:Cytoplasmic Structures / Q000737:chemistry* / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles; D008105:Liver Cirrhosis, Biliary / Q000097:blood; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary; D011506:Proteins; D012315:RNA Caps / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012694:Serine / Q000737:chemistry
chemical_list: D000906:Antibodies; D001324:Autoantigens; C507914:EDC4 protein, human; D005456:Fluorescent Dyes; D007211:Indoles; D009687:Nuclear Proteins; D011506:Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012694:Serine; C007293:DAPI