Ge-1 is a central component of the mammalian cytoplasmic mRNA processing body.
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.
Yu
Jiang Hong
JH
Department of Medicine, Havard Medical School, the Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Charlestown, MA 02129, USA.
Yang
Wei-Hong
WH
Gulick
Tod
T
Bloch
Kenneth D
KD
Bloch
Donald B
DB
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
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