RNA thermometer
An RNA thermometer (or RNA thermosensor) is a
In general, RNA thermometers operate by changing their
RNA thermometers, along with
Examples of RNA thermometers include FourU,[3] the Hsp90 cis-regulatory element,[4] the ROSE element,[5] the Lig RNA thermometer,[6] and the Hsp17 thermometer.[7]
Discovery
The first temperature-sensitive RNA element was reported in 1989.
The term "RNA thermometer" was not coined until 1999,[11] when it was applied to the rpoH RNA element identified in Escherichia coli.[12] More recently, bioinformatics searches have been employed to uncover several novel candidate RNA thermometers.[13] Traditional sequence-based searches are inefficient, however, as the secondary structure of the element is much more conserved than the nucleic acid sequence.[13]
Distribution
Most known RNA thermometers are located in the
Though predominantly found in
Structure
RNA thermometers are structurally simple and can be made from short RNA sequences; the smallest is just 44 nucleotides and is found in the mRNA of a heat-shock protein, hsp17, in Synechocystis species PCC 6803.[18][19] Generally these RNA elements range in length from 60 to 110 nucleotides[20] and they typically contain a hairpin with a small number of mismatched base pairs which reduce the stability of the structure, thereby allowing easier unfolding in response to a temperature increase.[21]
Detailed structural analysis of the ROSE RNA thermometer revealed that the mismatched bases are actually engaged in nonstandard basepairing that preserves the helical structure of the RNA (see figure). The unusual basepairs consist of G-G, U-U, and UC-U pairs. Since these noncanonical base pairs are relatively unstable, increased temperature causes local melting of the RNA structure in this region, exposing the Shine-Dalgarno sequence.[17]
Some RNA thermometers are significantly more complex than a single hairpin, as in the case of a region found in CspA mRNA which is thought to contain a pseudoknot, as well as multiple hairpins.[22][23]
Synthetic RNA thermometers have been designed with just a simple single-hairpin structure.[24] However, the secondary structure of such short RNA thermometers can be sensitive to mutation, as a single base change can render the hairpin inactive in vivo.[25]
Mechanism
RNA thermometers are found in the
A specific example of an RNA thermometer motif is the FourU thermometer found in
Though typically associated with heat-induced protein expression, RNA thermometers can also regulate cold-shock proteins.
RNA thermometers sensitive to temperatures of 37 °C can be used by pathogens to activate infection-specific genes.[14] For example, the upregulation of prfA, encoding a key transcriptional regulator of virulence genes in Listeria monocytogenes, was demonstrated by fusing the 5′ DNA of prfA to the green fluorescent protein gene; the gene fusion was then transcribed from the T7 promoter in E. coli, and fluorescence was observed at 37 °C but not at 30 °C.[29]
Implications for the RNA world hypothesis
The RNA world hypothesis states that RNA was once both the carrier of hereditary information and enzymatically active, with different sequences acting as biocatalysts, regulators and sensors.[30] The hypothesis then proposes that modern DNA, RNA and protein-based life evolved and selection replaced the majority of RNA's roles with other biomolecules.[2]
RNA thermometers and riboswitches are thought to be
Other examples
- Hsp90 cis-regulatory element regulates hsp90 in Drosophila, increasing the translation rate of the heat shock protein at high temperatures.[4]
- The ibpAB operon of E. coli is predicted to contain two co-operative RNA thermometers: a ROSE element and the IbpB thermometer.[33]
- ROSE1 and ROSEAT2 are found in hyphomicrobiales Bradyrhizobium japonicum and Agrobacterium tumefaciens respectively. They exist in the 5′ UTR of HspA mRNA, and repress heat shock protein translation at physiological temperatures.[5][34]
- Cyanobacterial RNA thermometers
- Intergenic RNA thermometer
- Neisseria RNA thermometers
- Lig RNA thermometer
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