The case of the missing allosteric 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.…”

“…Even if an aptamer exhibits the desired ligand-binding specificity and affinity, the aptamer needs to be fused to an mRNA such that expression is regulated by the ligand. A common choice is to fuse an aptamer to a self-cleaving ribozyme to create a ligand-mediated self-destructing RNA, but such arrangements are very rare among natural riboswitches [43]. Perhaps molecular engineers would be better served by exploiting aptamers to regulate alternative splicing [165,166], as is observed with natural eukaryotic riboswitches [95][96][97][98][99][100][101] (Box 5).…”

“…Descriptions of riboswitch mechanism diversity are provided elsewhere [6,9,15,44,101], and it seems likely that additional types remain to be discovered. Surprisingly, almost no riboswitch aptamers are known that allosterically regulate the activity of an adjacent ribozyme (Box 5) [43].…”

Structure and mechanism of the methyltransferase ribozyme MTR1

“…Natural ribozymes are known to catalyse a narrow range of chemical reactions, while a large diversity of natural riboswitches are known to bind nucleotide metabolites, including S-adenosylmethionine (SAM), cobalamin, nicotinamide adenine dinucleotide (NAD + ), flavine mononucleotide (FMN), and purines, such as guanine and pre-queuosine (preQ1). 1,2 Several of these metabolites are essential coenzymes for methyl transferase enzymes in contemporary biology. These coenzymes are thought to have evolved in the RNA world, and primordial RNA catalysts may have utilized coenzymes to achieve greater chemical diversity.…”

A highly sensitive and selective fluoride sensor based on a riboswitch-regulated transcription coupled with CRISPR-Cas13a tandem reaction

“…Functional nucleic acids, 1,2 such as aptamers, [3][4][5][6][7] riboswitches, 8,9 ribozymes, [10][11][12][13] and DNAzymes, [14][15][16][17][18] have emerged as a major class of sensors for on-site and real-time detections in applications such as environmental monitoring 19,20 and point-of-care diagnostics [21][22][23][24] of a wide range of targets with high selectivity. [25][26][27][28][29][30] Despite the progress, these functional nucleic acid sensors work well mainly for positively charged or neutral molecules.…”