Riboswitches: from ancient gene-control systems to modern drug targets.

Running an efficient metabolism requires finely tuned regulatory systems to make sure that the correct metabolites are produced at the necessary times and in the appropriate concentrations. To achieve this, cells make use of numerous molecular sensors and switches to control the production and function of enzymes. Interestingly, not all small-molecule sensors are made of proteins. Many bacteria and some species of archaea and eukarya are known to make use of metabolite-binding gene control elements made of RNA, called riboswitches [1, 2]. These RNAs are nature’s versions of small-molecule-binding aptamers, which are engineered RNAs created using methods first described by Larry Gold [3] and Jack Szostak [4] in the early 1990s. Most riboswitches reside in where they form selective binding pockets or aptamers for their target metabolites without the requirement for protein factors. Folding changes brought about by RNA-metabolite complex subsequently modulate the level of expression of a protein coding region usually located immediately downstream. At least 20 classes

[1]  F H CRICK,et al.  The genetic code. , 1962, Scientific American.

[2]  M. Mack,et al.  The RFN riboswitch of Bacillus subtilis is a target for the antibiotic roseoflavin produced by Streptomyces davawensis , 2009, RNA biology.

[3]  R. Breaker,et al.  The structural and functional diversity of metabolite-binding riboswitches. , 2009, Annual review of biochemistry.

[4]  Ronald R. Breaker,et al.  Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression , 2009, RNA biology.

[5]  A. Serganov,et al.  Coenzyme recognition and gene regulation by a flavin mononucleotide riboswitch , 2009, Nature.

[6]  R. Montange,et al.  Riboswitches: emerging themes in RNA structure and function. , 2008, Annual review of biophysics.

[7]  R. Breaker,et al.  Antibacterial lysine analogs that target lysine riboswitches. , 2007, Nature chemical biology.

[8]  R. Breaker,et al.  Riboswitches as antibacterial drug targets , 2006, Nature Biotechnology.

[9]  Patricio Jeraldo,et al.  The Genetic Code , 2006 .

[10]  R. Breaker,et al.  Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. , 2005, Chemistry & biology.

[11]  H. White Coenzymes as fossils of an earlier metabolic state , 1976, Journal of Molecular Evolution.

[12]  Thomas A Steitz,et al.  RNA, the first macromolecular catalyst: the ribosome is a ribozyme. , 2003, Trends in biochemical sciences.

[13]  Jeffrey E. Barrick,et al.  Metabolite-binding RNA domains are present in the genes of eukaryotes. , 2003, RNA.

[14]  R. Breaker,et al.  An mRNA structure that controls gene expression by binding FMN , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Evgeny Nudler,et al.  Sensing Small Molecules by Nascent RNA A Mechanism to Control Transcription in Bacteria , 2002, Cell.

[16]  Ronald R. Breaker,et al.  Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression , 2002, Nature.

[17]  Ali Nahvi,et al.  Genetic control by a metabolite binding mRNA. , 2002, Chemistry & biology.

[18]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[19]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[20]  S A Benner,et al.  Modern metabolism as a palimpsest of the RNA world. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  S. Benner,et al.  Natural selection, protein engineering, and the last riboorganism: rational model building in biochemistry. , 1987, Cold Spring Harbor symposia on quantitative biology.

[22]  W. Gilbert Origin of life: The RNA world , 1986, Nature.

[23]  L. Orgel Evolution of the genetic apparatus. , 1968, Journal of molecular biology.

[24]  F. H. C. CRICK,et al.  Origin of the Genetic Code , 1967, Nature.