Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Schizophrenia gene discovered

06.08.2013
Working independently from different perspectives, geneticists from Finland and biochemists from Würzburg have researched the molecular mechanisms of schizophrenia and cognitive impairment. They have concluded that their results complement each other perfectly.

There is something peculiar, and macabrely so, that makes the population of Finland so interesting to geneticists: during the colonization of the country it is likely that there were several natural disasters that claimed many victims among the settlers and drastically reduced their number. This, combined with the fact that the individual settler tribes scarcely mingled with each other, has meant that in Finland today certain genetic defects occur much more frequently than in other European countries.

The risk rises in the north

This peculiarity is clear to see on a map. For example, the number of people with a neurodevelopmental disorder increases steadily the farther one moves from the south-west to the north-east of the country. Anyone who grows up in the far north-east, for instance, is approximately twice as likely to suffer from schizophrenia as a resident of the capital, Helsinki. The risk is lower in the region west of Helsinki. The same applies to other forms of cognitive disorders.

In the search for the genetic bases of schizophrenia and differing degrees of cognitive impairment, geneticists from Finland have now made a discovery: they were able to show that the loss of a gene on chromosome 22 roughly doubles the risk of developing one of these diseases. In their study of the population of north-eastern Finland they identified a defect in the so-called TOP3ß gene that is responsible for the faulty development of the brain in those affected.

Two teams, one research subject

TOP3ß: this, coincidentally, is the exact same gene, or protein, that scientists at the University of Würzburg’s Department of Biochemistry have long been researching. So, when they heard of the work by the Finnish geneticists led by Aarno Palotie and Nelson Freimer, Professor Utz Fischer, as the head of the department, and his colleagues Georg Stoll, Conny Brosi, and Bastian Linder immediately contacted Helsinki. As the ensuing discussions revealed, the projects of the two teams complement each other perfectly. A preliminary report on the results has been published online in the journal Nature Neuroscience.

“The TOP3ß protein is a topoisomerase that most biochemists do not expect to learn much more about and therefore dismiss out of boredom,” says Utz Fischer. It is well-known that topoisomerases are responsible for the spatial organization of DNA; until now they have not been associated with unknown exciting properties. Fischer and his team are looking at the enzyme for a different reason: “For some time now we have been exploring a complex composed of three proteins, the so-called TTF complex,” says Fischer.

Responsible for autism and schizophrenia

The central element of this complex is a protein with the name TDRD3. Attached to its ends are the TOP3ß and FMRP proteins. This combination is quite something: a defect in the TOP3ß gene is now known to increase the risk of schizophrenia, while it has been recognized for some time that FMRP is associated with Fragile X syndrome – one of the most common causes of an inherited cognitive disorder in humans. Sufferers have differing degrees of diminished intelligence; quite a few exhibit autistic traits or have epileptic seizures. “The TTF complex therefore possesses two components whose absence triggers symptoms that sit at opposite ends of the scale for autism spectrum disorders,” explains Georg Stoll. Defects in the TOP3ß protein are linked to schizophrenia; damage to the FMRP protein increases the risk of autism.

What happens inside the cell

The Würzburg biochemists are interested in the TTF complex because they can use it to track how the information stored in DNA inside the cell nucleus is converted into proteins in the cytoplasm. “Our focus is on the fundamental question of how an mRNP is structured in the cell; this is a messenger RNA that is loaded with specific proteins,” explains Fischer. This structure is unique for every mRNP and determines its regulation upon transcription into proteins. Using the TTF complex as an example, the biochemistry team was able to uncover at least a few details of this process.

They found that the TDRD3 molecule binds to DNA in the cell nucleus via a protein-protein interaction and, in so doing, provides a link between the chromatin and the translation — in other words, the process by which genetic information is copied to mRNA molecules and the respective proteins are then synthesized. “This link was not known about before. It reveals one possible way in which the cell can specifically intervene in the fate of mRNA and how a dysregulation of mRNA can cause diseases,” says Fischer.

The impact on messenger RNA

TDRD3 also binds to mRNA – again via a protein-protein interaction. To achieve this, it docks onto the so-called exon junction complex, a molecule complex that is important in the processing, export, and quality control of RNA. The other components of the TTF complex, the TOP3ß and FMRP proteins, then also come into play, causing the corresponding pathologies if they are faulty.

“We suspect that, depending on which protein is missing, mRNA is sometimes upregulated and sometimes downregulated,” says Georg Stoll. So far, however, this is only a hypothesis, which the scientists are now keen to investigate in further experiments, but, he points out, it would explain why one extreme of an autism spectrum disorder occurs in one given situation, while the other extreme occurs in another.

The biochemists believe that the basic result of their work is important: “We have been able to demonstrate that the topoisomerase TOP3ß is active not only on DNA but also on RNA,” says Fischer. By so doing, the researchers have uncovered one way in which proteins use RNA to influence the reading of genetic information.

“Deletion of TOP3ß, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders”. Georg Stoll et al. Nature Neuroscience, published online August 4, 2013. doi:10.1038/nn.3484

Contact

Prof. Dr. Utz Fischer, T: +49 (0)931 31-84029,
e-mail: utz.fischer@biozentrum.uni-wuerzburg.de

Gunnar Bartsch | Uni Würzburg
Further information:
http://www.uni-wuerzburg.de

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>