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Pyrvinium Pamoate Changes Alternative Splicing Of The Serotonin Receptor 2c By Influencing Its Rna Structure, Manli Shen, Stanislav Bellaousov, Michael Hiller, Pierre De La Grange, Trevor O. Creamer, Orit Malina, Ruth Sperling, David H. Mathews, Peter Stoilov, Stefan Stamm
Pyrvinium Pamoate Changes Alternative Splicing Of The Serotonin Receptor 2c By Influencing Its Rna Structure, Manli Shen, Stanislav Bellaousov, Michael Hiller, Pierre De La Grange, Trevor O. Creamer, Orit Malina, Ruth Sperling, David H. Mathews, Peter Stoilov, Stefan Stamm
Molecular and Cellular Biochemistry Faculty Publications
The serotonin receptor 2C plays a central role in mood and appetite control. It undergoes pre-mRNA editing as well as alternative splicing. The RNA editing suggests that the pre-mRNA forms a stable secondary structure in vivo. To identify substances that promote alternative exons inclusion, we set up a high-throughput screen and identified pyrvinium pamoate as a drug-promoting exon inclusion without editing. Circular dichroism spectroscopy indicates that pyrvinium pamoate binds directly to the pre-mRNA and changes its structure. SHAPE (selective 2'-hydroxyl acylation analysed by primer extension) assays show that part of the regulated 5'-splice site forms intramolecular base pairs that …