Riboswitches

In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA. Thus, a mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the concentrations of its effector molecule. The discovery that modern organisms use RNA to bind small molecules, and discriminate against closely related analogs, expanded the known natural capabilities of RNA beyond its ability to code for proteins, catalyze reactions, or to bind other RNA or protein macromolecules.

The original definition of the term "riboswitch" specified that they directly sense small-molecule metabolite concentrations. Although this definition remains in common use, some biologists have used a broader definition that includes other cis-regulatory RNAs. However, this article will discuss only metabolite-binding riboswitches.

Most known riboswitches occur in bacteria, but functional riboswitches of one type (the TPP riboswitch) have been discovered in plants and certain fungi. TPP riboswitches have also been predicted in archaea, but have not been experimentally tested.

Prior to the discovery of riboswitches, the mechanism by which some genes involved in multiple metabolic pathways were regulated remained mysterious. Accumulating evidence increasingly suggested the then-unprecedented idea that the mRNAs involved might bind metabolites directly, to affect their own regulation. These data included conserved RNA secondary structures often found in the untranslated regions (UTRs) of the relevant genes and the success of procedures to create artificial small molecule-binding RNAs called aptamers. In 2002, the first comprehensive proofs of multiple classes of riboswitches were published, including protein-free binding assays, and metabolite-binding riboswitches were established as a new mechanism of gene regulation.

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