May 2013

Story of a donut and a death machine

Fig. 1 from the De Lay et al Minireview in The Journal of Biological Chemistry 
Fig. 1 from the De Lay et al Minireview shows the important protein players in sRNA-mediated gene repression. Click on the image to see a larger, more easily readable version of it. 

Not all RNAs code for proteins; instead, some of them play crucial roles in regulating other RNAs that do encode for proteins. One such class of noncoding RNA found in bacteria are those that are 50 to 300 nucleotides long, called small RNAs. Under stress, these sRNAs are induced and base pair with target messenger RNAs, leading to a positive effect (stabilization/activation) or a negative effect (repression/degradation) on mRNA translation.
In 1975, A.J. Wahba and co-workers first identified a host factor for the RNA phage Qβ, named Hfq, a protein that more recently has been shown to function as an RNA chaperone in bacteria. Hfq is a donut-shaped protein that binds sRNA on one face and mRNA on the other. This Hfq complex is essential for sRNA-based gene regulation in bacteria. This complex is an RNA death machine. At its heart is an endonuclease, RNAse E; interacting with its four arms are auxiliary functions to improve and regulate the degradation of RNA. The Hfq complex interacts with this RNaseE complex.
In a recent review in The Journal of Biological Chemistry, Nicholas De Lay, Daniel J. Schu and Susan Gottesman at the National Cancer Institute explain how Hfq, RNase E and other proteins act in collusion with sRNAs to affect negatively mRNA translation and stability.
The authors describe multiple pathways by which mRNA decay occurs, thus affecting subsequent translation regulation. In eukaryotes, RNA-induced silencing complex and Argonaute proteins play roles similar to those of  bacterial Hfq and RNaseE complex. Though the machinery in bacteria and eukaryotes varies, the authors conclude that the use of sRNAs to control mRNA translation is an underlying common theme that provides “well regulated control of translation, using machinery that is sensitive to the state of the mRNA, its ability to be translated, and that can be tuned in multiple ways to fit the physiological requirements.”

Preethi ChanderPreethi Chander ( is a health science analyst at the National Institutes of Health.


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