Regulation of mRNA stability through a pentobarbital-responsive element
Bünyamin Akgül1, Chen-Pei D Tu
1Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 108 Althouse Lab, University Park, PA 16802, USA.
Archives of Biochemistry and Biophysics
|January 20, 2007
Summary
Pentobarbital stabilizes Drosophila gstD21 mRNA by affecting turnover, not just transcription. A specific 59-nucleotide element in the 3'UTR mediates this pentobarbital-responsive stabilization.
Area of Science:
- Molecular Biology
- Genetics
- Pharmacology
Background:
- Pentobarbital is a general anesthetic that can influence gene expression.
- The Drosophila glutathione S-transferase D21 (gstD21) gene's mRNA is normally unstable but stabilized by pentobarbital.
- This stabilization occurs beyond transcriptional activation, suggesting post-transcriptional regulation.
Purpose of the Study:
- To identify cis-acting elements in gstD21 mRNA responsible for pentobarbital-mediated stabilization.
- To elucidate the mechanism of pentobarbital's effect on gstD21 mRNA turnover.
Main Methods:
- Constructing transgenic flies expressing chimeric gstD21 mRNA with heterologous UTRs.
- Analyzing mRNA decay intermediates to pinpoint stabilization elements.
- Assessing the impact of the gstD21 3'UTR on reporter transcript stability under pentobarbital treatment.
Main Results:
- The native UTRs of gstD21 mRNA are necessary for its inherent instability and pentobarbital-induced stabilization.
- Decay intermediates lacking the 3'UTR were not stabilized by pentobarbital.
- The gstD21 3'UTR alone conferred a 1.6-fold stabilization to a reporter transcript under pentobarbital treatment.
- Analysis suggested a polysome-associated mRNA decay pathway.
Conclusions:
- A 59-nucleotide pentobarbital-responsive element (PBRE) located in the gstD21 3'UTR is responsible for the mRNA stabilization.
- Pentobarbital regulates gstD21 mRNA stability through a post-transcriptional mechanism involving the 3'UTR.
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