Key result
Naphthyridine carbamate tetramer (NCTn) stabilized the engineered pseudoknot structure in mRNA and activated -1 ribosomal frameshifting both in vitro and in human cells.
NCTn-inducible -1PRF may serve as an important component of the synthetic biology toolbox for precise control of gene expression.
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May expand synthetic mRNA control tools; leaves open clinical translation from cell and animal data.
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.
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Matsumoto et al. (2018) studied this question. Naphthyridine carbamate tetramer (NCTn) was evaluated on Activation of -1 ribosomal frameshifting (-1PRF). Naphthyridine carbamate tetramer (NCTn) stabilized the engineered pseudoknot structure in mRNA and activated -1 ribosomal frameshifting both in vitro and in human cells.
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