RNA sensors: novel regulators of gene expression.

RNA-mediated control can evolve far more rapidly than mechanisms that rely on proteins, creating selective advantages in adaptive gene regulation. Recently, evidence has emerged that messenger RNA is a source of cis-acting RNA elements that sense external signals and thereby regulate gene expression. With exquisite specificity, metabolite-sensing riboswitches control the formation or translation of prokaryotic mRNA. In eukaryotes, RNA sensors in human antiviral cytokine genes that encode tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been shown to activate strongly the RNA-dependent protein kinase PKR, a stress kinase that is also activated by double-stranded RNA--a hallmark of viral infection. These cis-acting RNA elements in the TNF-alpha and IFN-gamma transcripts function as sensors of intracellular PKR levels and regulate gene expression at the level of mRNA splicing and translation, respectively. Although RNA sensors in bacteria may be remnants of an ancient RNA world, it is likely that they form an integral part of higher eukaryotic genomes as well.