RRC ID 54050
Author Matsumoto S, Caliskan N, Rodnina MV, Murata A, Nakatani K.
Title Small synthetic molecule-stabilized RNA pseudoknot as an activator for -1 ribosomal frameshifting.
Journal Nucleic Acids Res
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.
Volume 46(16)
Pages 8079-8089
Published 2018-9-19
DOI 10.1093/nar/gky689
PII 5063821
PMID 30085309
PMC PMC6144811
MeSH Animals Base Sequence / genetics Carbamates / chemical synthesis Carbamates / chemistry Frameshifting, Ribosomal / genetics* Gene Expression Regulation / drug effects* Mammary Tumor Virus, Mouse / genetics Mice Naphthyridines / chemical synthesis Naphthyridines / chemistry Nucleic Acid Conformation / drug effects Protein Biosynthesis / drug effects Protein Biosynthesis / genetics Protein Isoforms / genetics RNA / chemistry RNA / drug effects* RNA, Messenger / genetics RNA, Viral / genetics Small Molecule Libraries / chemical synthesis Small Molecule Libraries / chemistry Small Molecule Libraries / pharmacology* Synthetic Biology
IF 11.502
Times Cited 7
Human and Animal Cells HeLa(RCB0007) 293(RCB1637)