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

Saki Matsumoto, Neva Caliskan, Marina V. Rodnina, Asako Murata, Kazuhiko Nakatani

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8079-8089
Number of pages11
JournalNucleic acids research
Volume46
Issue number16
DOIs
Publication statusPublished - Sept 19 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics

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