An RNA thermometer.

Abstract

The expression of a conserved set of heat shock proteins is induced when cells grown at low temperatures are shifted to higher temperatures. Heat shock proteins are molecular chaperones or proteases that act to fold, translocate, or degrade proteins that appear to be misfolded or denatured upon heat shock. The heat shock response has been the focus of much research, and how the temperature signal is sensed and transduced to the biosynthetic machinery has been studied extensively. The s (RpoH) alternative s-factor, which is encoded by the rpoH gene, is a key regulator of the Escherichia coli heat shock response (for review, see Gross 1996; Missiakas et al. 1996). Upon a temperature shift from 30°C to 42°C, s accumulates and directs RNA polymerase to the promoters of the heat shock genes (Fig. 1). Earlier studies showed that both increased synthesis and stability lead to the increased levels of s. The activity of s and its association with RNA polymerase are also modulated by heat shock. A great deal has been learned about the increased stability of s in response to increased temperature. During normal growth the half-life of s is ∼1 min; upon upshift the half-life is increased to ∼5 min. Interestingly, the heat shock proteins DnaK, DnaJ, GrpE and HflB, whose expression is regulated by s, function to destabilize s. These proteins interact with s, sequestering it away from RNA polymerase and targeting it for degradation. Misfolded proteins that accumulate after heat shock appear to titrate the DnaK, DnaJ, and GrpE chaperones and the HflB protease away from s. Therefore, the pool of misfolded proteins is thought to be one measure of elevated temperature in the cell. Increased s synthesis was known to occur at the level of translation. However, although the E. coli heat shock response has been under investigation for many years, the thermometer signaling the need for increased translation was not known. In this issue Morita et al. (1999) show that the secondary structure of the rpoH mRNA itself is a thermosensor. These investigators present strong correlations between the expression of rpoH–lacZ fusions and the predicted and actual thermostability of the rpoH mRNA secondary structure. In addition, rpoH–lacZ expression levels correlate with the formation of rpoH mRNA–30S ribosome– tRNAf Met complexes. Thus, the melting of the rpoH mRNA secondary structure at high temperature leads to ribosome binding and increased s synthesis. Here, I summarize the findings that led to this conclusion. I also contrast the rpoH mRNA with other proposed RNA and protein thermometers.