Discovery and characterization of the first non-coding RNA that regulates gene expression, micF RNA: A historical perspective.

The first evidence that RNA can function as a regulator of gene expression came from experiments with prokaryotes in the 1980s. It was shown that Escherichia coli micF is an independent gene, has its own promoter, and encodes a small non-coding RNA that base pairs with and inhibits translation of a target messenger RNA in response to environmental stress conditions. The micF RNA was isolated, sequenced and shown to be a primary transcript. In vitro experiments showed binding to the target ompF mRNA. Secondary structure probing revealed an imperfect micF RNA/ompF RNA duplex interaction and the presence of a non-canonical base pair. Several transcription factors, including OmpR, regulate micF transcription in response to environmental factors. micF has also been found in other bacterial species, however, recently Gerhart Wagner and Jörg Vogel showed pleiotropic effects and found micF inhibits expression of multiple target mRNAs; importantly, one is the global regulatory gene lrp. In addition, micF RNA was found to interact with its targets in different ways; it either inhibits ribosome binding or induces degradation of the message. Thus the concept and initial experimental evidence that RNA can regulate gene expression was born with prokaryotes.