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Small RNA as Modular Kit

Even pathogenic bacteria can suffer from stress - when they are attacked by the immune system of their host, for instance. How salmonella bacteria react to such stress conditions is described by Würzburg infection biologists in the scientific journal PNAS.

Salmonella is a type of bacteria that can cause severe diarrhea in humans. On entering the digestive tract, these bacteria will not proliferate unchallenged: The immune system attacks the intruders - with peptides, for instance. These peptides are small proteins, which tear holes in the envelope of the bacteria.

The salmonella react immediately to such envelope damage: Among other things, they produce a small RNA molecule (RybB-sRNA), which promptly prevents the synthesis of about ten proteins in the bacterial cell. All of the proteins in question fulfill biological functions on the envelope of the bacteria.

A reasonable mechanism: "In this way, the salmonella bacteria quickly help themselves. Since the outer membrane is full of holes, the proteins would not be able to persist there and fulfill their function," explains Kai Papenfort of the Institute for Molecular Infection Biology at the University of Würzburg. Thus, the small RNA molecule avoids a waste of protein resources.

RNA start region binds precursors for proteins

But how does the small RNA manage to regulate the production of multiple proteins all at the same time? An answer to this question is given by the Würzburg researchers in the current issue of the scientific journal PNAS: "The start region of the sRNA molecule binds the transcripts, which are a kind of precursor for all these proteins," says Professor Jörg Vogel, the head of the institute. "As soon as this happens, the protein production stops." To prove this, the researchers transferred this start region to other RNA molecules. As a result, the modified molecules also brought the production of the ten proteins to a halt.

Without change in the evolution of the bacteria

With this research, the Würzburg scientists have shown for the first time: Even small RNA molecules possess clearly defined regions to which a regulatory function can be attributed. Previously, this was known to be true only for proteins, but not for "simpler" molecules such as RNA. "RNA also consists of functional units, which can be newly arranged on the basis of a modular design principle," explains Professor Vogel.

Furthermore, the regulatory region represents an RNA section, which has not changed in the evolution of the bacteria. This means: "This RNA is present not only in salmonella, but also in many other pathogenic bacteria and it always has the same function," explains Kai Papenfort.

A molecular structure, which has not undergone any evolutionary change - this suggests that it must be essential. It may be a factor, which is indispensable to the bacteria for the infection process and could play a role in triggering the disease. To clarify whether this is the case is the next objective of the Würzburg researchers. Ultimately, the start region of RybB-sRNA might even become a starting point for new drugs.

Basic research on small RNA

The team of Professor Jörg Vogel conducts basic research on small RNA molecules, the chains of which consist of about 100 components (small RNA, short: sRNA). This particular type of RNA regulates life processes in bacteria and more highly developed cells. Besides salmonella, the Würzburger scientists also used helicobacter as a model organism - a bacterium, which can cause stomach cancer.

"Evidence for an autonomous 5' target recognition domain in an Hfq-associated small RNA", Kai Papenfort, Marie Bouvier, Franziska Mika, Cynthia M. Sharma, and Jörg Vogel; PNAS, published online on 8 November 2010, doi 10.1073/pnas.1009784107

Contact person

Dr. Kai Papenfort, Institute for Molecular Infection Biology at the University of Würzburg, T +49 (0)931 31-81230, kai.papenfort@uni-wuerzburg.de

idw :: 16.11.2010

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