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 1401-amino-acid protein. Ge-1 contains an N-terminal WD40 motif and C-terminal domains characterized by a repeating ψ(X2–3) motif. Ge-1 co-localized with previously identified P-body components, including proteins involved in mRNA decapping (DCP1a and DCP2) and the autoantigen GW182. 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.
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Footnotes
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↵5 Patient Ge was initially believed to have Sjögren’s syndrome. She was subsequently found to have abnormal liver function tests and anti-mitochondrial antibodies, and the diagnosis of primary biliary cirrhosis was established.
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↵6 In the original report, a sequencing error at nt 3671 resulted in a frameshift and failure to appreciate the C-terminal 213 amino acids of Ge-1.
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↵4 These authors contributed equally to this work.
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Article and publication are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2142405.
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- Accepted August 29, 2005.
- Received June 20, 2005.
- Copyright 2005 by RNA Society