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
|
Resource |
Human and Animal Cells |
HeLa(RCB0007)
293(RCB1637) |