4 Riboswitches and the RNA World

Abstract

Aptamers are RNA or DNA molecules that fold into higher-ordered structures and form complexes with specific ligands. Typically, we think of an aptamer as an engineered molecule that was created to bind its target ligand by using a directed evolution process (Ellington and Szostak 1990; Tuerk and Gold 1990). More recently, natural examples of aptamers that bind small molecules have been found as part of RNA genetic control elements called riboswitches (Mandal and Breaker 2004a; Nudler and Mironov 2004). Both engineered aptamers and riboswitch aptamers show high affinity and selective binding of targets, properties that were once assumed only to be manifest by proteins.

The initial descriptions of engineered aptamers were striking for two reasons. First, they provided fresh demonstrations that nucleic acids could be subjected to Darwinian evolution in a test tube. Second, these along with the many reports that followed helped prove that nucleic acids have an enormous untapped potential for forming complex shapes, and that many different molecules could be selectively recognized by RNA and DNA (Gold et al. 1995; Osborne and Ellington 1997). Furthermore, these findings fit well with more robust versions of the RNA World theory (Woese 1967; Crick 1968; Orgel 1968; Gilbert 1986), which holds that aptamers might have existed alongside a diversity of ribozymes to allow early life forms to attain a complex metabolic state long before proteins had emerged (Benner et al. 1989; Hirao and Ellington 1995).

The recent discoveries of riboswitches in bacteria that selectively respond to fundamental metabolites provide researchers...