Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 16, Pages 8079-8089Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky689
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Funding
- JSPS KAKENHI [26000007, 15K01820, 265460]
- Research Program of 'Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials' in 'Network Joint Research Center for Materials and Devices'
- Max Planck Society
- Deutsche Forschungsgemeinschaft [SFB 860]
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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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