Related Experiment Videos
Increased rate of degradation of c-myc mRNA in interferon-treated Daudi cells
Abstract:
The recent observation made in our laboratory that cellular myc (c-myc) mRNA has a very short half-life in a variety of normal and transformed human cells emphasized the potential importance of post-transcriptional regulation of c-myc gene expression. Jonak and Knight [Jonak, G. J. & Knight, E., Jr. (1984) Proc. Natl. Acad. Sci. USA 81, 1747-1750] have reported a selective reduction of c-myc mRNA accumulation in lymphoblastoid Daudi cells treated with human beta interferon. This provided a suitable situation in which to examine a possible action of negative modulators of c-myc expression at the level of mRNA stability. Our results confirm the observation by Jonak and Knight that c-myc mRNA level is depressed in cells treated with beta interferon and extend it to alpha 2 interferon. Furthermore, we now demonstrate that interferon has no effect on c-myc transcription rate in isolated nuclei but rather reduces the half-life of its mRNA. Conversely, we show that it increases the level of HLA-A2 mRNA by stimulating its transcription.
Insights
Interferon reduces cellular myc (c-myc) mRNA levels by decreasing mRNA stability, not transcription. This post-transcriptional regulation affects gene expression in human cells.
Area of Science:
- Molecular Biology
- Gene Regulation
- Immunology
Background:
- Cellular myc (c-myc) mRNA exhibits a short half-life in human cells.
- Post-transcriptional regulation is crucial for c-myc gene expression.
- Human beta interferon selectively reduces c-myc mRNA accumulation in Daudi cells.
Purpose of the Study:
- To investigate the mechanism by which interferon affects c-myc mRNA levels.
- To determine if interferon modulates c-myc expression at the transcriptional or post-transcriptional level.
- To examine the effect of alpha 2 interferon on c-myc mRNA stability.
Main Methods:
- Treatment of lymphoblastoid Daudi cells with human beta and alpha 2 interferons.
- Measurement of c-myc mRNA accumulation.
- Analysis of c-myc transcription rates in isolated nuclei.
- Assessment of mRNA half-life.
- Evaluation of HLA-A2 mRNA levels and transcription.
Main Results:
- Interferon treatment confirmed to depress c-myc mRNA levels.
- Interferon was found to have no effect on c-myc transcription rate.
- Interferon was demonstrated to reduce the half-life of c-myc mRNA.
- Interferon was shown to increase HLA-A2 mRNA levels by stimulating its transcription.
Conclusions:
- Interferons negatively regulate c-myc gene expression post-transcriptionally by reducing mRNA stability.
- Interferons differentially regulate gene expression, decreasing c-myc mRNA while increasing HLA-A2 mRNA.
- This study highlights the role of mRNA stability in controlling oncogene expression.