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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>