Title

Aptamer-enabled uptake of small molecule ligands

Publication Date

10-24-2018

Department

Ames Laboratory; Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of; Biomedical Sciences; Mathematics

Campus Units

Ames Laboratory, Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Biomedical Sciences, Mathematics

OSTI ID+

1481863

Report Number

IS-J 9802

DOI

10.1038/s41598-018-33887-w

Journal Title

Scientific Reports

Volume Number

8

Issue Number

1

First Page

15712

Abstract

The relative ease of isolating aptamers with high specificity for target molecules suggests that molecular recognition may be common in the folds of natural RNAs. We show here that, when expressed in cells, aptamers can increase the intracellular concentrations of their small molecule ligands. We have named these aptamers as DRAGINs (Drug Binding Aptamers for Growing Intracellular Numbers). The DRAGIN property, assessed here by the ability to enhance the toxicity of their ligands, was found for some, but not all, aminoglycoside aptamers. One aptamer protected cells against killing by its ligand. Another aptamer promoted killing as a singlemer and protected against killing as a tandemer. Based on a mathematical model, cell protection vs. killing is proposed as governed by aptamer affinity and access to the inner surface of the cell membrane, with the latter being a critical determinant. With RNA molecules proposed as the earliest functional polymers to drive the evolution of life, we suggest that RNA aptamer-like structures present in primitive cells might have selectively concentrated precursors for polymer synthesis. Riboswitches may be the evolved forms of these ancient aptamer-like “nutrient procurers”. Aptamers with DRAGIN capability in the modern world could be applied for imaging cells, in synthetic cell constructs, or to draw drugs into cells to make “undruggable” targets accessible to small molecule inhibitors.

DOE Contract Number(s)

AC02-07CH11358

Language

en

Department of Energy Subject Categories

59 BASIC BIOLOGICAL SCIENCES

Publisher

Iowa State University Digital Repository, Ames IA (United States)

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