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 Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>