Small synthetic molecule-stabilized RNA pseudoknot as an activator for -1 
ribosomal frameshifting.

Matsumoto, S.; Calsikan, N.; Rodnina, M. V.; Murata, A.; Nakatani, K.

doi:10.1093/nar/gky689

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Small synthetic molecule-stabilized RNA pseudoknot as an activator for -1 ribosomal frameshifting.

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Rodnina, M. V.
Department of Physical Biochemistry, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Matsumoto, S., Calsikan, N., Rodnina, M. V., Murata, A., & Nakatani, K. (2018). Small synthetic molecule-stabilized RNA pseudoknot as an activator for -1 ribosomal frameshifting. Nucleic Acids Research, 46(16), 8079-8089. doi:10.1093/nar/gky689.

Cite as: https://hdl.handle.net/21.11116/0000-0001-EA7D-C

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.