Facebook, mySpace, Twitter, and RNA-based metabolic sensors: Remnants of ancient control machinery or ever-present control mechanism?

Social media and riboswitches? They might be more related than you think…. Today, Ruben talks about the ancient origins of riboswitches and poses interesting questions about their future.

If you were a teenager in the early 2000s, you probably used mySpace as your first social media. You might have even posted Emo-inspired pictures and used glittery GIFs. However, unfortunately for mySpace, Facebook was created in 2004 and soon after it started to rapidly overtake mySpace´s users, until 2008 when Facebook became the most used social platform worldwide. Other social media such as Twitter also remain active because it is specialized in a different type of social interaction: less about personal social connections and more about staying informed by following topics, conversations and people. These differences allowed Twitter to conserve their niche on an ever-growing sea of social media options.

This analogy came to my mind while reading about different sensing molecules. In order to survive and reproduce, organism have evolved mechanisms to sense and translate environmental signals as efficiently as possible. It is generally recognized that many of these mechanisms are protein-based molecules, which regulate gene expression in response to a chemical signal (e.g. transcription factors).

Although these protein-based sensing mechanisms explained the regulation of certain biological processes, they are not the only mechanism in action.This is often seen in the lack of correlation between transcriptome and proteome data. Insights into unknown interactions of RNA with metabolites led to the discovery of RNA sensing molecules able to control their own activity, so called: Riboswitches (Templeton et al., 2004).

Riboswitches work as RNA control elements that bind to a specific metabolite and once the RNA-metabolite interaction is done, the RNA structure changes to a new configuration, therefore influencing the transcription or translation of the gene. In this type of sensing mechanisms no direct interaction of a protein is observed, showing a complete different level of sensing and control.


Evidence of these control mechanisms was initially found exclusively in prokaryotic organism. Examples of riboswitches were later found in the other two domains of life: archaea and eukaryotes. One of the most conserved examples of a riboswitch in prokaryotic, eukaryotic and archaeal organisms is the thiamine pyrophosphate riboswitch (TPP-riboswitch), which is involved in thiamine synthesis and assimilation. The sensing domain (aptamer) and target metabolite appears to be fairly conserved through evolution, pointing to a possible ancient origin of this tool (Clingman & Ryder, 2012).

The fact that the TPP-riboswitch is fairly distributed between domains might hint at  a very old mechanism which could be traced to simpler RNA-based organisms. It is hypothesised  that most biological processes of these ancient organisms were carried out by RNA molecules (genetic storage, self-replication and catalysis), and consequently is it conceivable that RNA molecules were also the first genetic control and sensing tools?

Although there are several examples of other riboswitches involved in critical metabolic process in prokaryotes, identification in eukaryotes has been proven more difficult because of the increases complexity involved in gene expression of these organisms (Cheah et al, 2007).  Eukaryotic genes sometimes require more complex transcriptional processes (e.g. splicing) and genes are not often grouped into an operon, which reduces the versatility of prokaryotic riboswitches.

Perhaps evolution has preferred RNA-metabolite sensing for less complex organisms (prokaryotes), where the others (eukaryotes) preferred other forms of regulatory mechanisms, like protein-metabolite sensing.

Even though proteins might have replaced some of these RNA-based control systems, certain processes kept their supposedly original control mechanism where perhaps it was convenient enough, like the TPP sensor found in eukaryotes. If higher organisms truly lack more examples of riboswitches, perhaps the reason also rest in the fact that proteins are more stable and versatile molecules, with possible multiple function associated, pointing them as preferable   metabolite-sensing   tools for more complex organisms.

The detection of more riboswitches and RNA control tools in eukaryotes could open the possibility of new therapeutic and industrial strategies. This also may represent just the surface of more complicated RNA structures, which could be related to metabolic control and that currently are not understood due to its complexity.

Since most of the known riboswitches are in the prokaryotic domain, the question is still open. Are they more like mySpace, meaning they are vestiges of an ancient control machinery which have only been conserved for a handful of metabolic pathways? Or are they more like Twitter, conserved for a specific type of sensing and control mechanisms, and whose interactions have not been unveiled by the techniques used to study them. In this matter ‘omics’ approaches may help to identify novel examples about how metabolites affect posttranscriptional regulation.

Because of this evolutionary importance, modern organisms might have variations of what we know as riboswitches. Further investigation of riboswitches in different biological domains will help to understand the role of these control mechanisms and determine if they are as widespread as other well-known tools like transcription factors or if they are simply remnants of ancient machineries.



  •        Cheah, M. T., Wachter, A., Sudarsan, N., & Breaker, R. R. (2007). Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature, 447(7143), 497-500.
  •        Clingman, C. C., & Ryder, S. P. (2013). Metabolite sensing in eukaryotic mRNA biology. Wiley Interdisciplinary Reviews. RNA, 4(4), 387-396.
  •        Mandal, M., & Breaker, R. R. (2004). Gene regulation by riboswitches. Nature Reviews.Molecular Cell Biology, 5(6), 451-463.
  •        Templeton, G. W., & Moorhead, G. B. (2004). A renaissance of metabolite sensing and signaling: From modular domains to riboswitches. The Plant Cell, 16(9), 2252-2257.

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