Published online Nov 26, 2015. doi: 10.4331/wjbc.v6.i4.272
Peer-review started: June 11, 2015
First decision: August 25, 2015
Revised: September 5, 2015
Accepted: October 1, 2015
Article in press: October 8, 2015
Published online: November 26, 2015
Processing time: 165 Days and 7 Hours
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.
Core tip: The original discovery and characterization of the first non-coding RNA gene and its transcript was with prokaryotes in the 1980s. At that time the Escherichia coli micF RNA gene was characterized in terms of properties, its promoter region, and activation by environmental stress conditions; and the micF RNA transcript structure as well as the micF RNA/target messenger RNA duplex interaction were elucidated. This occurred over 5 years before the discovery of the first eukaryotic regulatory miRNA, which is not generally recognized. Prokaryotic and eukaryotic non-coding RNAs greatly differ in terms of RNA processing, but the basic principle of an RNA gene locus encoding a regulatory RNA that targets gene expression in trans via RNA/target RNA duplex formation is similar. Thus the concept and discovery of regulatory non-coding RNAs and their functions in messenger RNA inhibition originated with prokaryotes.