An mRNA structure that controls gene expression by binding S-adenosylmethionine

Abstract

Riboswitches are metabolite-binding RNA structures that serve as genetic control elements for certain messenger RNAs. These RNA switches have been identified in all three kingdoms of life and are typically responsible for the control of genes whose protein products are involved in the biosynthesis, transport or utilization of the target metabolite. Herein, we report that a highly conserved RNA domain found in bacteria serves as a riboswitch that responds to the coenzyme S-adenosylmethionine (SAM) with remarkably high affinity and specificity. SAM riboswitches undergo structural reorganization upon introduction of SAM, and these allosteric changes regulate the expression of 26 genes in Bacillus subtilis. This and related findings indicate that direct interaction between small metabolites and allosteric mRNAs is an important and widespread form of genetic regulation in bacteria.

Four RNA families with functional transient structures

“…85,86 They correspond to non-coding RNA structure elements located in the leader sequence of mRNA strands, which selectively bind certain metabolites to regulate the synthesis of downstream products relevant to this metabolite. [2][3][4]11,87 This regulatory response is achieved by the coordination between the embedded metabolite-binding aptamer domain and the expression platform which switches between alternative structures upon sensing a change in the aptamer domain when a metabolite binds. 3,4,11 The riboswitch can generally assume two mutually-exclusive structures -one metabolite-bound, and one metaboliteunbound.…”

“…[2][3][4]11,87 This regulatory response is achieved by the coordination between the embedded metabolite-binding aptamer domain and the expression platform which switches between alternative structures upon sensing a change in the aptamer domain when a metabolite binds. 3,4,11 The riboswitch can generally assume two mutually-exclusive structures -one metabolite-bound, and one metaboliteunbound. This ligand recognition via aptamer can sequentially affect the interaction between the mRNA and the translational or transcriptional apparatus.…”

“…88 The structure of the aptamer is typically evolutionarily conserved; for instance, the S-adenosylmethionine (SAM) riboswitch discussed in this paper is well conserved among bacteria species. 11 In SAM riboswitch, S box is the aptamer where the coenzyme SAM binds with high affinity, which often precedes a putative transcription terminator hairpin; the binding of SAM triggers an allosteric change that subsequently terminates the transcription. 11,89 Overall, a riboswitch assigns the same mRNA both a sensory and an action role without requiring an intermediate.…”

“…11 In SAM riboswitch, S box is the aptamer where the coenzyme SAM binds with high affinity, which often precedes a putative transcription terminator hairpin; the binding of SAM triggers an allosteric change that subsequently terminates the transcription. 11,89 Overall, a riboswitch assigns the same mRNA both a sensory and an action role without requiring an intermediate. 90 This amounts to a speedy and sensitive responsive mechanism that is able to sense the conditions of the cellular environment with an accuracy comparable to mechanisms involving protein factors.…”

“…6 Moreover, such transient structures can be employed to regulate gene expression either via translational control as exemplified in Levivirus 7,8 or via a transcriptional mechanism as exhibited by Tryptophan operon leader 9,10 and SAM riboswitch. 11 Last but not the least, transient structures incorporating the 5' flanking sequence are involved in adjusting the self-cleavage activity of HDV ribozyme, CPEB3 ribozyme and group I intron. 12,13 Recent statistical evidence suggests that some transient structures are evolutionarily conserved across homologous sequences thus confirming their potential functional importance.…”