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(Wagner) Bacterial sRNAs Roles and Mechanisms
(Wagner) Bacterial sRNAs Roles and Mechanisms
SYNOPSIS
Post-trancriptional control of gene expression has become a focus of attention in recent years. Small non-
coding RNAs play central roles in regulation of genes in all kingdoms of life – sometimes by titration of
regulatory proteins, but most often by antisense mechanisms. Based on genome-wide searches we know
today of ≈80 so-called small RNAs (sRNAs) encoded by the chromosome of the enterobacterium
Escherichia coli alone. Most sRNAs whose biological roles have been elucidated appear to be stress-related
[1]. For example, several sRNAs are transcriptionally upregulated when membrane stress is perceived
(MicA, MicC, MicF etc [2]). These sRNAs base-pair, aided by the RNA-binding protein Hfq, to their target
mRNAs to inhibit protein synthesis and, most often, to facilitate mRNA degradation [3]. All members of
this structurally and sequence-wise diverse group of sRNAs downregulates the synthesis of outer
membrane proteins (OMPs) to alleviate membrane stress. Regulation of OMP synthesis by sRNAs reveals
complexity: some targets are regulated by more than one sRNA, and one sRNA can regulate multiple
targets. Several other stresses in which sRNA regulation has been demonstrated are: oxidative stress, SOS/
DNA damage, sugar stress, cold shock, and iron stress.
The role of Hfq in sRNA-mediated regulation has been investigated intensely in many
laboratories. Yet, some fundamental question regarding its molecular mechanism of action and its
implication for the in vivo situation have not been fully addressed. Results from our group indicate that
most cis-encoded (and therefore fully target-complementary) sRNAs [6] do not require Hfq, whereas most
(but not all, e.g. IstR-1) trans-encoded sRNAs need Hfq for regulatory activity. Why this is so is yet
elusive. Secondly, the very tight binding of Hfq to sRNAs and target mRNAs (usually at nM Kd-values)
should create a problem in the cell, since Hfq must recycle rapidly to be available for newly synthesized
sRNAs. The question of Hfq cycling, and its rate-enhancing effect in the sRNA-target RNA binding
process, will be addressed in this talk.
ACKNOWLEDGEMENT
Work in our group is funded by VR (Swedish Science Research Council), EU-STREP FOSRAK, EU-
STREP-BacRNAs, EU-Marie Curie, and a Linnéus grant/VR.
REFERENCES
1. Romby, P., Vandernesch, F., and Wagner, E.G.H. (2006) Curr. Opin. Microbiol. 9, 229-236
2. Vogel, J., and Papenfort, K. (2006) Curr. Opin. Microbiol. 9, 605-611
3. Udekwu, K., Darfeuille, F., Vogel, J., Reimegård, J., Holmqvist, E. and Wagner, E.G.H. (2005) Genes
& Dev. 19, 2355-2366
4.Vogel, J., Argaman, L., Wagner, E.G.H. and Altuvia, S. (2004) Curr. Biol. 14, 2271-2276
5.Darfeuille, F., Unoson, C., Vogel, J. and Wagner, E.G.H. (2007) Mol. Cell 26, 381-392
6. Wagner, E.G.H., Altuvia, S., and Romby, P. (2002) Adv. Genet. 46, 361-398