An RNA thermometer (or RNA thermosensor) is a temperature-sensitive non-coding RNA molecule which regulates gene expression. RNA thermometers often regulate genes required during either a heat shock or cold shock response, but have been implicated in other regulatory roles such as in pathogenicity and starvation. In general, RNA thermometers operate by changing their secondary structure in response to temperature fluctuations. This structural transition can then expose or occlude important regions of RNA such as a ribosome binding site, which then affects the translation rate of a nearby protein-coding gene. RNA thermometers, along with riboswitches, are used as examples in support of the RNA world hypothesis. This theory proposes that RNA was once the sole nucleic acid present in cells, and was replaced by the current DNA → RNA → protein system. Examples of RNA thermometers include FourU, the Hsp90 cis-regulatory element, the ROSE element, the Lig RNA thermometer, and the Hsp17 thermometer. The first temperature-sensitive RNA element was reported in 1989. Prior to this research, mutations upstream from the transcription start site in a lambda (λ) phage cIII mRNA were found to affect the level of translation of the cIII protein. This protein is involved in selection of either a lytic or lysogenic life cycle in λ phage, with high concentrations of cIII promoting lysogeny. Further study of this upstream RNA region identified two alternative secondary structures; experimental study found the structures to be interchangeable, and dependent on both magnesium ion concentration and temperature. This RNA thermometer is now thought to encourage entry to a lytic cycle under heat stress in order for the bacteriophage to rapidly replicate and escape the host cell. The term 'RNA thermometer' was not coined until 1999, when it was applied to the rpoH RNA element identified in Escherichia coli. More recently, bioinformatics searches have been employed to uncover several novel candidate RNA thermometers. Traditional sequence-based searches are inefficient, however, as the secondary structure of the element is much more conserved than the nucleic acid sequence. Most known RNA thermometers are located in the 5' untranslated region (UTR) of messenger RNA encoding heat shock proteins—though it has been suggested this fact may be due, in part, to sampling bias and inherent difficulties of detecting short, unconserved RNA sequences in genomic data. Though predominantly found in prokaryotes, a potential RNA thermometer has been found in mammals including humans. The candidate thermosensor heat shock RNA-1 (HSR1) activates heat-shock transcription factor 1 (HSF1) and induces protective proteins when cell temperature exceeds 37 °C (body temperature), thus preventing the cells from overheating.