The Role of 3′ Poly(A) Tail Metabolism in Tumor Necrosis Factor-α Regulation
| Autor: | Eric K. Crawford, Jeffrey D. Hasday, J. E. Ensor, Indira Kalvakolanu |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
Cytoplasm Polyadenylation Stimulation Biology Biochemistry Monocytes Cell Line Mice Polysome Protein biosynthesis Animals Humans RNA Processing Post-Transcriptional Molecular Biology Protein Synthesis Inhibitors Messenger RNA Tumor Necrosis Factor-alpha Macrophages Cell Biology Molecular biology Alternative Splicing Gene Expression Regulation Cell culture Polyribosomes Protein Biosynthesis Tumor necrosis factor alpha Poly A |
| Zdroj: | Journal of Biological Chemistry. 272:21120-21127 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.272.34.21120 |
| Popis: | In unstimulated RAW 264.7 macrophage-like cells, tumor necrosis factor-alpha (TNF-alpha) mRNA was transcribed and accumulated in the cytoplasm, but the TNF-alpha transcripts failed to associate with polysomes, and TNF-alpha protein was not detected. Stimulation with lipopolysaccharide (LPS) induced an increase in TNF-alpha transcription, cytoplasmic TNF-alpha mRNA accumulation, polysome association, and secretion of TNF-alpha protein. This process was associated with a 200-nucleotide increase in the apparent length of the TNF-alpha mRNA. The difference in TNF-alpha mRNA size was caused by marked truncation of the 3' poly(A) tail in unstimulated cells. Fully adenylated TNF-alpha mRNA appeared within 15 min of LPS stimulation. We speculate that removal of the poly(A) tail blocks initiation of TNF-alpha translation in unstimulated macrophages. LPS inactivates this process, allowing synthesis of translatable polyadenylated TNF-alpha mRNA. |
| Databáze: | OpenAIRE |
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