Abstract
Gene control systems sometimes interpret multiple signals to set the expression levels of the genes they regulate. In rare instances, ligand-binding riboswitch aptamers form tandem arrangements to approximate the function of specific two-input Boolean logic gates. Here, we report the discovery of riboswitch aptamers for phosphoribosyl pyrophosphate (PRPP) that naturally exist either in singlet arrangements, or occur in tandem with guanine aptamers. Tandem guanine-PRPP aptamers can bind the target ligands, either independently or in combination, to approximate the function expected for an IMPLY Boolean logic gate to regulate transcription of messenger RNAs for de novo purine biosynthesis in bacteria. The existence of sophisticated all-RNA regulatory systems that sense two ancient ribonucleotide derivatives to control synthesis of RNA molecules supports the hypothesis that RNA World organisms could have managed a complex metabolic state without the assistance of protein regulatory factors.
Highlights
A variety of riboswitch classes regulate gene expression in response to the binding of specific metabolite or inorganic ion ligands (Roth and Breaker, 2009; Serganov and Nudler, 2013; Sherwood and Henkin, 2016)
To evaluate PRPP binding and riboswitch aptamer function, we examined a 106 nucleotide singlet aptamer arbitrarily derived from the purC gene of the bacterium Facklamia ignava (Figure 2A) by using in-line probing (Soukup and Breaker, 1999; Regulski and Breaker, 2008)
The structural changes selectively brought about by PRPP largely occur in regions equivalent to those previously implicated in ligand binding by guanidine-I (Nelson et al, 2017; Reiss et al, 2017; Battaglia et al, 2017) and ppGpp riboswitch classes
Summary
A variety of riboswitch classes regulate gene expression in response to the binding of specific metabolite or inorganic ion ligands (Roth and Breaker, 2009; Serganov and Nudler, 2013; Sherwood and Henkin, 2016). This strong bias in favor of RNA-like ligands strengthens the hypothesis (Nelson and Breaker, 2017; Breaker, 2010) that many of the widely-distributed riboswitch classes are direct descendants from the RNA World – a time before genetically-encoded protein biosynthesis (Gilbert, 1986; Benner et al, 1989) If this speculation is generally correct, we can expect that some of the most abundant riboswitch classes remaining to be discovered will regulate gene expression in response to the binding of other ancient RNA derivatives (Breaker, 2011). Upon further investigation of the RNA sequences, the phylogeny of organisms containing these RNAs, and the genes associated with each instance of the RNA, we concluded that ykkC subtype 2 RNAs were populated by multiple riboswitch classes that sensed distinct ligands
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