Imaginary Ribozymes

Abstract

Biocatalysis is dominated by protein enzymes, and only a few classes of ribozymes are known to contribute to the task of promoting biochemical transformations. The RNA World theory encompasses the notion that earlier forms of life made use of a much greater diversity of ribozymes and other functional RNAs to guide complex metabolic states long before proteins had emerged in evolution. In recent years, the discoveries of various classes of ribozymes, riboswitches, and other noncoding RNAs in bacteria have provided additional support for the hypothesis that RNA molecules indeed have the catalytic competence to promote diverse chemical reactions without the aid of protein enzymes. Herein, some of the most striking observations made from examinations of natural riboswitches that bind small ligands are highlighted and used as a basis to imagine the characteristics and functions of long-extinct ribozymes from the RNA World.

A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

“…Extant riboswitches can also provide clues about the organization of extinct ribozymes 46 . Riboswitches that utilize distal binding domains to accommodate a single ligand suggest how the folds of early ribozymes were organized to position substrates 46 . Our findings extend this concept to single-domain ribozymes.…”

Discovering riboswitches: the past and the future

“…Even with these challenges, we believe the current imperfect methods for counting and classifying riboswitches can yield important observations and predictions [14][15][16][17][40][41][42][43]. Of paramount interest is the task of predicting how many riboswitch classes remain to be discovered in extant species.…”

Recent progress in non-native nucleic acid modifications

“…The discovery of naturally occurring catalytic RNA molecules (ribozymes) predates the advent of SELEX but these combinatorial methods of in vitro selection have allowed the identification of DNA enzymes (DNAzymes) along with nucleic acid molecules capable of catalyzing a broad variety of chemical transformations. 451,471,518 The realisation that nucleic acid scaffolds required substantial concentrations of M 2+ cofactors for activity to compensate the dearth of functional groups present on the nucleobases and backbone, combined with the notorious fragility to nucleases, rapidly called for the introduction of modified nucleotides in SELEX experiments. 533 and have permitted (and will certainly continue) expansion of the catalytic repertoire of DNAzymes and ribozymes.…”