Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A New Connection between Metabolism and Regulation

22.12.2014

Heidelberg scientists discover modified ribonucleic acids in bacteria

In cells, ribonucleic acids (RNAs) are most commonly known as messengers or scaffold molecules, but they can also accelerate key biochemical reactions and regulate metabolic pathways. These regulatory RNAs were discovered just a few years ago.

In studies on bacteria, scientists from Heidelberg University have now found previously unknown modifications in the RNAs that contribute to their stability against the degradation mechanisms of the cell. Among other things, regulatory RNAs are associated with cancer development and bacterial infections. The findings of the research at the Institute of Pharmacy and Molecular Biotechnology were published in the journal “Nature”.

In bacteria, most of these regulatory RNAs act by binding other RNA molecules, e.g. messenger RNAs, thereby triggering the degradation of the resulting complexes. As a consequence, the bound RNAs are no longer available for the biosynthesis of proteins, Prof. Dr. Andres Jäschke of the Institute of Pharmacy and Molecular Biotechnology explains.

“So far, regulatory RNAs had been assumed to be composed of the four standard building blocks, the nucleotides A, C, G and U. We were now able to show that some regulatory RNAs in the gut bacterium Escherichia coli carry a particular modification at their ends that confers increased stability against the cell’s degradation machinery.” Furthermore, the team headed by Prof. Jäschke found an enzyme that can remove this modifying cap and release the previously protected RNA for degradation. According to Prof. Jäschke, the modifier is an “old acquaintance”, i.e. nicotinamide adenine dinucleotide (NAD), which assumes a key role in the metabolism of both bacteria and higher organisms.

These NAD-modified regulatory RNAs can be isolated by a novel method that was developed by chemist Dr. Hana Cahová and biotechnologist Dr. Marie-Luise Winz. In their approach, an enzyme from a marine mollusc and a technique known as “click chemistry” were used to label only the NAD-modified RNA molecules contained in a total RNA sample, while all others remained unaltered.

The labelled RNAs can thus be selectively isolated and identified by high-throughput sequencing and comparison with databases. “For many of the modified RNAs we identified, no biological function is known to date. Interestingly, others have been described in the context of cellular metabolism or associated with the bacterial response to ‘stress’ caused by extreme environmental conditions,” Andres Jäschke notes.

The scientists have now looked into the question why a bacterium modifies some of its regulatory RNAs with NAD. “As the chemical nature of the ends was known to be a key factor in the degradation of RNA by cellular enzymes, we assumed that the NAD modification might stabilize the RNA,” says biotechnologist Katharina Höfer. Together with biochemist Gabriele Nübel, she thus investigated several known degradation pathways.

The researchers could indeed demonstrate a significantly increased stabilisation against two modification and degradation enzymes. As it would be useful for the cell to cleave off the protective cap once its purpose is fulfilled, the scientists tested further enzymes and discovered what they were looking for yet again: one of the enzymes was able to remove NAD and thus initiate RNA degradation.

Andres Jäschke’s team suspect the attached NAD to have additional functions. “The nicotinamide adenine dinucleotide interacts with many proteins in a specific manner, so the NAD-RNAs might form protein complexes as well, which, in turn, might regulate various processes in the bacterium. In addition, NAD can occur in the cell in two different forms, namely in an oxidised and in a reduced one. The equilibrium between these two states may influence and modulate the biological function of NAD-RNAs,” Prof. Jäschke explains.

While protective caps at the ends of RNA have been known for decades in higher organisms, this is the first study to report a cap-like – but chemically different – structure in bacteria, according to the scientists. These investigations open up a new research area, as the biological functions and the mechanisms of this new modification now need to be clarified. “We are particularly interested to find out whether these NAD modifications are present in bacteria only or in higher organisms as well,” comments Andres Jäschke. “If this were a phenomenon specific to bacteria, it might provide clues for new antibacterial treatments.”

The research work was supported by fellowships from the Alexander von Humboldt Foundation and the Hartmut Hoffmann-Berling International Graduate School for Molecular and Cellular Biology (HBIGS) of Heidelberg University.

Original Publication:
Cahová, H., Winz, M.-L., Höfer, K., Nübel, K. & Jäschke, A.: NAD captureSeq indicates NAD as a bacterial cap for a subset of regulatory RNAs. Nature (22 December 2014), DOI 10.1038/nature14020

Internet information:
http://www.jaeschke.uni-hd.de

Contact:
Prof. Dr. Andres Jäschke
Institute of Pharmacy und Molecular Biotechnology
Phone +49 6221 54-4853
jaeschke@uni-hd.de

Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-heidelberg.de

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>