Fruit Fly Study Leads to New Understanding of How mRNA Regulates Gene Expression

A study on heat sensitivity in fruit flies has led to a new understanding of how gene expression is regulated by mRNAs in a fashion that is independent of both DNA and protein.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) were studying the genetic mechanism that controls the behavior of a mutant variety of Drosophila that was unusually sensitive to high temperatures. These flies carried a mutated copy of a gene called seizure (sei) that rendered them so sensitive to heat that a rise in temperature of even 10 degrees was sufficient to send them into seizures.

"When we looked at the sei gene, we noticed that there is another gene on the opposite strand of the double-stranded DNA molecule called pickpocket 29 (ppk29)," said senior author Dr. Yehuda Ben-Shahar, assistant professor of biology at the Washington University School of Medicine. "This was interesting because sei codes for a protein ‘gate’ that lets potassium ions out of the neuron and pickpocket 29 codes for a gate that lets sodium ions into the neuron."

The investigators generated a series of transgenic lines of Drosophila with different ratios of sei and ppk29. They reported in the March 18, 2014, online edition of the journal eLife that mRNA originating from ppk29 was regulating the mRNA from the sei gene. The regulatory component of ppk29 was identified as the untranslated 3' UTR end of the mRNA strand. When this section of ppk29 mRNA formed a double stranded segment with complementary DNA from sei it resulted in the destruction of the sei strand through the combination of the Dicer enzyme and RISC (RNA-induced silencing complex) assembly. Thus, the gene coding a sodium channel was found to regulate the expression of the potassium channel gene.

“Our findings show that mRNAS, which are typically thought to act solely as the template for protein translation, can also serve as regulatory RNAs, independent of their protein-coding capacity,” said Dr. Ben-Shahar. “They are not just messengers but also actors in their own right.”

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