Abstract
A bacterial noncoding RNA motif almost exclusively associated with pnuC genes was uncovered using comparative sequence analysis. Some PnuC proteins are known to transport nicotinamide riboside (NR), which is a component of the ubiquitous and abundant enzyme cofactor nicotinamide adenine dinucleotide (NAD+). Thus, we speculated that the newly found “pnuC motif” RNAs might function as aptamers for a novel class of NAD+-sensing riboswitches. RNA constructs that encompass the conserved nucleotides and secondary structure features that define the motif indeed selectively bind NAD+, nicotinamide mononucleotide (NMN), and NR. Mutations that disrupt strictly conserved nucleotides of the aptamer also disrupt ligand binding. These bioinformatic and biochemical findings indicate that pnuC motif RNAs are likely members of a second riboswitch class that regulates gene expression in response to NAD+ binding.
Highlights
Most known riboswitch classes sense compounds that are derived from RNA monomers or their precursors (McCown et al 2017)
We speculated that the pnuC motif might represent the conserved aptamer domain of a novel riboswitch class that senses and responds to a molecule in the NAD+ biosynthetic pathway
Our findings indicate that pnuC motif RNAs are selective sensors of nicotinamide riboside (NR) or its 5′-modified derivatives such as nicotinamide mononucleotide (NMN) and NAD+
Summary
Most known riboswitch classes sense compounds that are derived from RNA monomers or their precursors (McCown et al 2017). A recent report (Malkowski et al 2019) presented bioinformatic, genetic, and biochemical data supporting the hypothesis that nadA motif RNAs (Weinberg et al 2017) function as riboswitches for the coenzyme NAD+. This discovery helped overcome the strange circumstance that NAD+, one of the most abundant, ubiquitous, and ancient coenzymes in biology, had no identified corresponding riboswitch classes (Breaker 2011; Malkowski et al 2019). Most other coenzymes are sensed by one or more distinct riboswitch classes that regulate genes related to the transport, synthesis, or use of these molecules (McCown et al 2017)
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