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Regulation of human tissue factor expression by mRNA turnover
S M Ahern1, T Miyata, J E Sadler
1Department of Medicine, Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, Missouri 63110.
The Journal of Biological Chemistry
|January 25, 1993
Summary
Researchers identified specific sequences in tissue factor mRNA responsible for its rapid degradation. This finding sheds light on the regulation of blood coagulation initiation by controlling mRNA stability.
Area of Science:
- Molecular Biology
- Biochemistry
- Hematology
Background:
- Tissue factor initiates blood coagulation and is normally absent from blood-contacting cells.
- Upon induction, tissue factor mRNA exhibits rapid degradation with a half-life of 0.75-1.5 hours.
Purpose of the Study:
- To investigate the cellular mechanisms underlying the rapid turnover of human tissue factor mRNA.
- To identify specific sequences within the tissue factor mRNA that confer rapid degradation.
Main Methods:
- Utilized chimeric tissue factor.beta-globin constructs in stably transfected mouse NIH/3T3 cells.
- Employed a transiently inducible c-fos promoter to avoid transcriptional inhibitors.
- Analyzed mRNA degradation kinetics and the role of specific mRNA sequences.
Main Results:
- Identified sequences within the final 600 nucleotides of tissue factor mRNA responsible for rapid degradation.
- The destabilizing element's activity depended on its specific sequence, not just AU content.
- mRNA degradation was inhibited by actinomycin D, and superinduced by cycloheximide.
Conclusions:
- Specific sequences at the 3' end of tissue factor mRNA, resembling AU-rich elements, mediate its rapid turnover.
- This regulation is crucial for controlling the expression of tissue factor and, consequently, blood coagulation initiation.