Degradation of targeted mRNAs in Escherichia coli: regulation by a small antisense RNA.

Abstract

In this issue of Genes & Development, Masse et al. (2003a) show that a small antisense RNA (saRNA) triggers mRNA degradation via a pathway in which the saRNA is also consumed. The stoichiometric binding of the saRNA to its mRNA target thus appears to activate the degradation of both RNAs (coupled degradation). The physical interaction of complementary polynucleotides is arguably the fundamental chemical principle underlying molecular genetics. It is the most important feature of the structure of double-stranded DNA, and it is at the heart of the mechanism by which tRNA decodes mRNA to synthesize protein. The article by Masse et al. (2003a) reports novel findings on the action of a chromosome-encoded saRNA in the regulation of gene expression. They show that RyhB, an saRNA, triggers mRNA degradation via a pathway in which RyhB is degraded together with its target mRNA. Similar results were obtained with two other saRNAs. Thus, it seems likely that RyhB will serve as a model for saRNAs that activate mRNA degradation. Biological regulatory mechanisms involving antisense RNA have been recognized for many years in Escherichia coli. However, until recently, the known antisense RNAs were encoded by extrachromosomal elements such as transposons, plasmids, and bacteriophage. With the current renaissance in interest in small noncoding RNAs, a surprising number of putative small regulatory RNAs (50–100), encoded on the E. coli chromosome, have recently been described. An important factor in the discovery of these RNAs was the availability of the complete genome sequence of E. coli and related bacteria such as Salmonella. This genomic information facilitated searches based, in part, on sequence conservation in noncoding regions of the chromosome. It is only now that the function of some of the newly discovered RNAs is being elucidated. Although it seems reasonable to believe that the chromosome-encoded saRNAs and the classical antisense RNAs from transposons, plasmids, and bacteriophage act by similar mechanisms, I will argue that there could be some significant differences. This perspective is based on the accompanying research article by Masse et al. (2003a). As a reference for recent developments on small regulatory RNAs in E. coli, I highly recommend the review by Susan Gottesman that was published in Genes & Development last year (Gottesman 2002). In this perspective, I will describe the antisense RNAs from transposons, plasmids, and bacteriophage that have been characterized over the past twenty years (classical antisense), then introduce the chromosome-encoded antisense RNAs that have been discovered recently (renaissance antisense). After that, I will briefly discuss some differences between these two families of antisense RNA, then discuss the work in the Masse et al. (2003a) article and its implications for the role of the chromosome-encoded antisense RNAs in mRNA degradation.