Riboswitch

In molecular biology, a riboswitch is a part of an mRNA molecule that can directly bind a small target molecule, and whose binding of the target affects the gene's activity. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, depending on the presence or absence of its target molecule.

Some riboswitches activate their gene when binding to the target, while others repress it. Riboswitches also differ as to their mechanism of control. Known riboswitches operate through transcription termination, translation initiation or self-cleavage (i.e. the riboswitch is a ribozyme that cleaves itself in a metabolite-dependent manner).

Most known riboswitches occur in eubacteria, but functional riboswitches of one type (the THI element) have been discovered in eukaryotes. Sequences similar to known riboswitches have also been found in archaea.

Riboswitches are a demonstration that naturally occurring RNA can bind small molecules, a capability that many previously believed was the domain of proteins or artificially constructed RNAs called aptamers. The existence of riboswitches in all domains of life therefore adds some support to the RNA world hypothesis, which holds that life originally existed using only RNA, and proteins came later; this hypothesis requires that all critical functions performed by proteins could be performed by RNA.

The following riboswitches are known (information on the first six from Vitreschak, 2004):

• RFN-element, which binds flavin mononucleotide to regulate riboflavin biosynthesis and transport.
• THI-element, which binds thiamin pyrophosphate to regulate thiamin biosynthesis and transport, as well as transport of similar metabolites
• B12-element, which binds adenosylcobalamin (related to vitamin B12) to regulate cobalamin biosynthesis and transport of cobalamin and similar metabolites, and other genes.
• S-box, which binds S-adenosyl methionine to regulate methionine biosynthesis and transport
• G-box, which binds purines to regulate purine metabolism and transport
• L-box/lysine riboswitch, which binds lysine to regulate lysine biosynthesis, catabolism and transport.
• glmS riboswitch, which binds glucosamine-6-phosphate to regulate glucosamine-6-phosphate synthetase (glmS) genes. This riboswitch is also a ribozyme.
• gcvT riboswitch, which binds glycine to regulate glycine metabolism genes, including the use of glycine as an energy source. As of 2004, this riboswitch is the only known natural RNA that exhibits cooperative binding.

Although the genetic pathways in which riboswitches are involved have been studied for decades, the existence of riboswitches has only recently been found. This oversight may relate to an assumption that genes are regulated by proteins, not by the mRNA transcript itself. Now that riboswitches are a known mechanism of genetic control, it is reasonable to speculate that more riboswitches will be found.

References

• A.G. Vitreschak, D.A. Rodionov, A.A. Mironov and M.S. Gelfand (2004) "Riboswitches: the oldest mechanism for the regulation of gene expression?", TRENDS in Genetics, 20 (1): 44-50. (A review paper. Not as focussed on the RNA world hypothesis as the title suggests.) article in PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14698618)
• N. Sudarsan, J.E. Barrick and R.R. Breaker (2003), "Metabolite-binding RNA domains are present in the genes of eukaryotes", RNA, 9:644-647. (The authors computationally discover a THI element-like sequence in plants and fungi, and show that it binds thiamin pyrophosphate in vitro.) article in PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12756322)