Dr. Poul Valentin-Hansen and colleagues at the University of Southern Denmark report that a small RNA, called Spot 42, functions by an antisense mechanism to differentially regulate gene expression in the galactose operon.
The E. coli galactose operon is a cluster of four contiguous genes that are expressed as a group and encode enzymes that regulate galactose sugar metabolism. Like all bacterial operons, the four gal genes (galE, T, K, and M) are transcribed into one polycistronic mRNA message. Interestingly though, although all four gal genes are translated from this one polycistronic message, the relative synthesis of the encoded enzymes differs depending upon metabolic conditions.
Although this discoordinate expression of the galactose operon was characterized more than 20 years ago, this report by Dr. Valentin-Hansen and colleagues provides the first mechanistic insight into the process.
Dr. Valentin-Hansen and colleagues have discovered that Spot 42, a small, 109-nucleotide RNA whose physiological role has eluded scientists for nearly 30 years, mediates discoordinate expression of the galactose operon. According to this study, Spot 42 acts as an antisense RNA that binds to a sequence of the GalK mRNA region to repress translation by interfering with ribosome binding. This way, GalK enzyme synthesis can be specifically down-regulated without compromising the production of the other Gal enzymes.
This work answers two long-standing biological questions, namely, how is discoordinate expression of the E. coli galactose operon regulated, and what is the function of Spot 42 RNA. Furthermore, the study provides a valuable example of small RNA-mediated regulation of the bacterial genome.