A Decade of Riboswitches

Abstract

Riboswitches were discovered in 2002 in bacteria as RNA-based intracellular sensors of vitamin derivatives. During the last decade, naturally occurring RNA sensor elements have been found to bind a range of small metabolites and ions and to exert regulatory control of transcription, translation, splicing, and RNA stability. Extensive biochemical, structural, and genetic studies have established the basic principles underpinning riboswitch function in all three kingdoms of life with implications for developing antibiotics, designing new molecular sensors, and integrating riboswitches into synthetic circuits.

Structural and mechanistic insights into prokaryotic energy-coupling factor transporters

“…In many cases, ribo switches are used to regulate the expression of ECF transporters. Riboswitches are sequence motifs that bind metabolites and are found upstream of the coding region in several mRNAs 30 . Binding results in alteration of the mRNA structure, which affects transcription or translation.…”

How RNA acts as a nuclease: some mechanistic comparisons in the nucleolytic ribozymes

“…In marked contrast, the potential catalytic resources of RNA are limited to four similar nucleobases, ribose with a secondary alcohol (2'-hydroxyl) and an anionic phosphodiester with associated hydrated metal ions that can bind sitespecifically (inner-sphere complex) or more dynamically in atmospheric mode. In addition, RNA is an excellent ligand for many small molecules (exemplified by the riboswitches (8,9)) and ribozymes can recruit additional molecules as coenzymes (10) or reactants (11).…”

Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures

“…Structured RNAs have numerous functions in a cell, including catalyzing the elongation of the amino acid chain in protein synthesis by rRNA (Noller et al 1992;Ban et al 2000), catalyzing pre-mRNA splicing by self-splicing introns (Kruger et al 1982;Fica et al 2013), regulating gene expression by siRNA (Fire et al 1998), and regulating gene expression in response to ligands using riboswitches (Nahvi et al 2002;Winkler et al 2004;Serganov and Nudler 2013). RNA secondary structure, defined as the set of A-T, C-G, and G-U canonical pairs in an RNA structure, is a resolution that has proven useful for studying RNA.…”

“…Further, in many functional RNAs, the secondary structure changes as part of the function. One example of this is riboswitches, in which presence of a ligand causes a secondary structure change to modulate transcription, translation, or splicing (Serganov and Nudler 2013). Accurate estimates of RNA switching could also be highly useful in synthetic biology applications, where circuits can be made entirely of RNA, which serves as both a messenger and an effector (Davidson and Ellington 2007).…”