T cell receptor (TCR) engagement leads to activation-induced splicing of tumor necrosis factor (TNF) nuclear pre-mRNA
| Autor: | C. Garrison Fathman, Ju-Fay Chang, Jane R. Parnes, Yang Yang |
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| Rok vydání: | 1998 |
| Předmět: |
Transcription
Genetic RNA splicing T-Lymphocytes Immunology Receptors Antigen T-Cell T cells TNF Biology Lymphocyte Activation 03 medical and health sciences Mice 0302 clinical medicine Gene expression Protein biosynthesis RNA Precursors Immunology and Allergy Animals 030304 developmental biology Regulation of gene expression 0303 health sciences Messenger RNA Mice Inbred BALB C Tumor Necrosis Factor-alpha T-cell receptor Articles pre-mRNA Molecular biology Gene Expression Regulation Tumor necrosis factor alpha Precursor mRNA transcription 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | Inducible gene expression is primarily regulated at the level of transcription. Additional steps of “processing” pre-mRNA, involved in the regulation of induced gene expression, have not been previously reported. Here we report a novel mechanism of “activation-induced splicing” of preexisting tumor necrosis factor (TNF) message (pre-mRNA) in naive T lymphocytes after engagement of the T cell receptor (TCR), which still occurs after inhibition of transcription. Expression of TNF has been previously demonstrated to be regulated at both the transcriptional and translational levels. However, neither the large pool of TNF mRNA observed in activated T cells nor TNF protein production, which peaks very shortly after activation, can be solely attributed to increased transcription. Evidence is presented that activation-induced splicing of TNF pre-mRNA plays a significant role in the rapid production of TNF seen in activated T cells. Activation triggers processing of TNF pre-mRNA that has accumulated in naive T cells (before activation-induced transcription), and the mature TNF mRNA is translocated to the cytoplasm for rapid translation and protein production. This novel form of activation-induced splicing of TNF may allow T cells to mount an immediate response to activation stimuli under physiological conditions. |
| Databáze: | OpenAIRE |
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