Are you feeling a chill?

One of the interesting aspects of RNA biology is the functioning of structured RNAs as regulatory elements, in particular as sensors that detect changes in environment and transduce the information into a change in gene expression.  One interesting class of such RNAs are the so-called riboswitches.  These are RNAs that typically bind to a ligand, much as an in vitro-selected RNA may bind to a chemical (such as an amino acid). Binding changes the structure of the RNA, leading to changes in transcription, stability of the RNA, or translatability of the RNA.

Riboswitches may bind small molecule ligands.  Alternatively, they may sense temperature.  This occurs because many RNA structures can be rather sensitive to changes in temperature, owing to the tendency of some secondary structures to become disrupted at physiologically meaningful temperatures.  A recent study extends the realm of RNA thermometers to include the sensing of cold temperatures, and adds a new twist to the nature of the riboswitch.  In this study, the authors studied the regulatory motif of the E. coli cspA gene; this gene is a cold-shock gene, whose expression increases with lower temperature.  This regulation may be attributed to in part to the 5′-untranslated part of the cspA mRNA. This work showed that low temperature promotes an RNA fold that enhances translation and RNA stability. Interestingly, this fold requires much (most) of the cspA mRNA; in other words, the whole mRNA is a sort of RNA thermometer that senses low temperature. The authors propose that the structural variations reflect co-transcriptional folding of the RNA, and that two different pathways (and end products) are traversed in cells growing at normal and low temperatures.

From the summary of the paper:

Highlights

• cspA mRNA adopts different conformations before and after cold shock
• The cold-shock structure results from stabilization of a folding intermediate
• The cold-shock structure is more efficiently translated than the 37°C structure

Summary

Cold induction of cspA, the paradigm Escherichia coli cold-shock gene, is mainly subject to posttranscriptional control, partly promoted by cis-acting elements of its transcript, whose secondary structure at 37°C and at cold-shock temperature has been elucidated here by enzymatic and chemical probing. The structures, which were also validated by mutagenesis, demonstrate that cspA mRNA undergoes a temperature-dependent structural rearrangement, likely resulting from stabilization in the cold of an otherwise thermodynamically unstable folding intermediate. At low temperature, the “cold-shock” structure is more efficiently translated and somewhat less susceptible to degradation than the 37°C structure. Overall, our data shed light on a molecular mechanism at the basis of the cold-shock response, indicating that cspA mRNA is able to sense temperature downshifts, adopting functionally distinct structures at different temperatures, even without the aid of trans-acting factors. Unlike with other previously studied RNA thermometers, these structural rearrangements do not result from melting of hairpin structures.

The citation:

Giuliodori AM, Di Pietro F, Marzi S, Masquida B, Wagner R, Romby P, Galerzi CO, Pon CL. 2010. The cspA mRNA Is a Thermosensor that Modulates Translation of the Cold-Shock Protein CspA. Mol. Cell 37, 21-33. 10.1016/j.molcel.2009.11.033