Abstract
Programmed -1 ribosomal frameshifting (-1PRF) is a recoding mechanism to make alternative proteins from a single mRNA transcript. -1PRF is stimulated by cis-acting signals in mRNA, a seven-nucleotide slippery sequence and a downstream secondary structure element, which is often a pseudoknot. In this study we engineered the frameshifting pseudoknot from the mouse mammary tumor virus to respond to a rationally designed small molecule naphthyridine carbamate tetramer (NCTn). We demonstrate that NCTn can stabilize the pseudoknot structure in mRNA and activate -1PRF both in vitro and in human cells. The results illustrate how NCTn-inducible -1PRF may serve as an important component of the synthetic biology toolbox for the precise control of gene expression using small synthetic molecules.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence / genetics
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Carbamates / chemical synthesis
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Carbamates / chemistry
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Frameshifting, Ribosomal / genetics*
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Gene Expression Regulation / drug effects*
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Mammary Tumor Virus, Mouse / genetics
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Mice
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Naphthyridines / chemical synthesis
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Naphthyridines / chemistry
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Nucleic Acid Conformation / drug effects
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / genetics
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Protein Isoforms / genetics
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RNA / chemistry
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RNA / drug effects*
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RNA, Messenger / genetics
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RNA, Viral / genetics
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Synthetic Biology
Substances
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Carbamates
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Naphthyridines
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Protein Isoforms
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RNA, Messenger
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RNA, Viral
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Small Molecule Libraries
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RNA