Title

Stringency of antisense regulation varies based on volatility of mRNA target region

Conference Dates

July 14-18, 2019

Abstract

Bacteria can regulate gene expression by transcribing antisense RNA to interfere with protein translation. Antisense has been shown to control a wide variety of prokaryotic proteins, including membrane proteins, protein toxins, and proteins involved in transport and metabolism. This type of regulation can be used in the production of biologics to optimize the health of the culture and maximize production of the desired product. We examined naturally occurring antisense to enhance design principles for product optimization. We found that the level of secondary structure fluctuation of the antisense binding site varied depending on the function of the target. We hypothesized that stringency of regulation by naturally evolved antisense was driven by the impact of the target molecule on cellular survival. Specifically, high stringency was important for toxin-antitoxin systems where survival depended on high levels of control. Toxin-antitoxin systems rely on effective antisense to prevent the translation of self-damaging proteins. Antisense-based systems regulating transport and metabolism potentially benefited from less stringent antisense control. Basal levels of antisense-regulated proteins involved in metabolic processes could allow for quick adaptation to changing nutrient conditions. More than fifty naturally occurring sense/antisense pairs were analyzed to demonstrate that antisense binding sites correlate to the level of stringency needed in regulating the target protein.

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