The folding of even short RNA molecules in a random library can produce a huge number of possible macromolecular structures. Using this principle, we have designed selections to seek non-coding RNA transcripts capable of interfering with specific macromolecules such as transcription factors in living bacterial cells. Here we show that such selections can uncover an unexpected class of RNAs. In the present case, we report short RNA transcripts whose expression confers bacterial resistance to the antibiotic spectinomycin. We provide evidence that such RNAs cause drug resistance by direct antibiotic binding, demonstrating a class of spectinomycin-specific functional molecular decoys built from RNA.
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