Gerhart Wagner

Department of Cell and Molecular Biology, Uppsala University. Home Page

Research Interest: Regulatory RNAs in bacteria and elsewhere

This research group is headed by professor Gerhart Wagner at the department of Cell and Molecular Biology, located at the Biomedical Center. Our work is concerned with the many roles that small RNAs play in fundamental life processes. From recent work in many laboratories throughout the world it has become clear that RNA molecules - in addition to their well-known roles in information transfer and protein synthesis - carry out regulatory functions.

In recent years, the identification of new "riboregulators" has been a focus of the group's activities. Today, more than 70 such small, putative regulatory RNAs (sRNAs) are known to be encoded by the chromosome of the enterobacterium E. coli alone. What are all these RNAs doing? We are presently involved in an effort to learn about their biological roles and to understand the nuts and bolts of their regulatory mechanisms.

Antisense RNAs are a special class of sRNAs. They are often found in plasmids where they regulate copy number, conjugation or post-segregational killing. These sRNAs base-pair to target RNAs to regulate their functions. We have extensively studied the CopA/CopT (antisense/target) RNA copy control system of plasmid R1 in previous years. This has given us deep insights into the contributions of RNA structure elements to regulatory efficiency and specificity.

Only a few chromosomally encoded sRNAs have so far been functionally characterized. The emerging pattern shows that most of them act by antisense mechanisms (often aided by specific helper proteins) to control genes involved in stress responses and modulation of cell surface properties. In pathogenic bacteria, RNAs are occassionally involved in regulating virulence traits, either directly or, by promoting stress tolerance, indirectly.

Our group is a partner (in one case, coordinator) of two EU-networks. FOSRAK is concerned with small RNAs as regulators in a cross-kingdom analysis and comparison. Here, we draw from the similarities, but also the particular properties of small RNAs in bacteria, protists, plants and animals. Most eukaryotes use special antisense RNA variants called microRNAs to regulate important life processes.

These microRNAs act in the context of ribonucleoprotein complexes to regulate translation or stability of mRNAs. Additionally, eukaryotic systems also support RNA interference, another (related) mechanism that "silences" genes post-transcriptionally. Also in this case, very short RNAs (siRNAs) are involved. They are generated from longer double-stranded RNAs, enter a so-called RISC-complex and promote specific degradation of target RNAs guided by base-pairing.

BacRNAs, the second network, addresses the roles of sRNAs specifically in pathogenic bacteria and is aimed at an in-depth understanding of virulence gene regulation by small RNAs, but also at future therapeutic strategies.

Our research is supported by grants from Vetenskapsrˆ€det, FORMAS, EU-FOSRAK, EU-BacRNAs.

Five Selected Publications

Argaman, L., Hershberg, R., Vogel, J., Bejerano, G.; Wagner, E.G.H., Margalit, H. & Altuvia, S. (2001) Novel small RNA-encoding genes in the intergenic regions of Escherichia coli. Curr. Biol. 11, 941-950. [Faculty of 1000: "Must Read"]

Vogel, J., Bartels, V., Slagter-Jäger, J.G., Hüttenhofer, A. & Wagner, E.G.H. (2003) RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria. Nucleic Acids Res. 31, 6435-6443.

Vogel, J., Argaman, L., Wagner, E.G.H., & Altuvia, S. (2004) The small RNA IstR inhibits synthesis of an SOS-induced toxic peptide. Curr. Biol. 14, 2271-2276.

Wagner, E.G.H. (2005) RNA - Molekylen som kan stänga av DNA (RNA - the molecule that can shut off genes; popular science article). Forskning och Framsteg. 1, 16-20.

Udekwu, K., Darfeuille, F., Vogel, J., Reimegård, J., Holmqvist, E. & Wagner, E.G.H. (2005) Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA. Genes & Dev. 19, 2355-2366. [Faculty of 1000: "Must Read"]