Navigation Links
Molecular mechanisms underlying the prevention of autoim-munity by Roquin revealed
Date:7/14/2014

The Roquin protein, discovered in 2005, controls T-cell activation and differentiation by regulating the expression of certain mRNAs. In doing so, it helps to guarantee immunological tolerance and prevents immune responses against the body's own structures that can lead to autoimmune disease. Roquin is thus an immune regulator. Autoimmune diseases affect between five and ten per cent of the population. They usually occur as a result of complex environmental influences when a genetic predisposition exists. Only in rare cases the development of the disease is determined by a single mutated gene. However, a single mutation in the Roquin gene in a mouse model was shown to be responsible for the development of the autoimmune disease systemic lupus erythematosus. This mutation in the Roquin protein also led to a high susceptibility to type 1 diabetes and rheumatoid arthritis and induced angioimmunoblastic T-cell lymphoma.

Elucidation of the three-dimensional structure of the Roquin-RNA complex

An interdisciplinary team comprising the research groups led by Prof. Michael Sattler, Dr. Dierk Niessing and Prof. Vigo Heissmeyer at the Helmholtz Zentrum Mnchen, Ludwig-Maximilian University (LMU) and the Technische Universitt Mnchen (TUM) has now revealed unprecedented insight into how Roquin recognizes its RNA binding partner and thereby controls T-cell functions. To this end, the scientists Dr. Andreas Schlundt, Gitta Heinz, and Dr. Robert Janowski used the X-ray crystallography platform of the Helmholtz Zentrum Mnchen to determine the spatial structure of the RNA binding domain of Roquin when bound to its RNA target. The interaction of Roquin with additional RNA binding partners was studied in solution using nuclear magnetic resonance (NMR) spectroscopy at the Bavarian NMR Center, a joint research infrastructure of the Helmholtz Zentrum Mnchen and TUM. Furthermore, the researchers could confirm the biological significance of the molecular recognition of the RNA by studying Roquin-dependent gene regulation in cellular systems.

The results obtained reveal for the first time the molecular interactions with which roquin recognizes a binding motif in a gene's mRNA. "To our surprise, these results indicate that a greater range of binding modes plays an important functional role for the gene regulation in T-cells," says Prof. Michael Sattler. "Thus, our findings suggest that Roquin regulates a larger number of genes than was previously assumed," Dr. Niessing adds. In addition to the mRNAs with optimal recognition motifs, which are tightly bound and predominantly regulated by Roquin, there is a potentially much larger number of mRNAs which are more weakly bound, but nevertheless regulated by Roquin. "On the basis of these findings we will now focus on understanding how Roquin levels are regulated in T-cells, since strong and weakly bound target mRNAs will experience a principally different regulation when the availability of the protein varies" explains Prof. Vigo Heissmeyer.

Basis for developing treatment

Defining the molecular interplay between Roquin and RNA is a prerequisite for con-trolling the function of Roquin and using its role for therapeutic strategies to treat autoimmune diseases. To this end, the scientists are now planning follow-up studies to find out how the function of Roquin can be manipulated.


'/>"/>

Contact: Prof. Dr. Michael Sattler
sattler@helmholtz-muenchen.de
49-893-187-3800
Helmholtz Zentrum Mnchen - German Research Center for Environmental Health
Source:Eurekalert

Related biology news :

1. Researchers uncover molecular pathway through which common yeast becomes fungal pathogen
2. Beyond the microscope: Identifying specific cancers using molecular analysis
3. 2012 Forecast for US Molecular Diagnostics Market Now Available From Global Information Inc.
4. 5th Annual Advances in Biomolecular Engineering Symposium
5. PNAS: Precise molecular surgery in the plant genome
6. Molecular spectroscopy tracks living mammalian cells in real time as they differentiate
7. Hitting snooze on the molecular clock: Rabies evolves slower in hibernating bats
8. The activity of a bacterial effector protein seen in molecular detail
9. How bacteria change movement direction in response to oxygen: Molecular interactions unravelled
10. MARC travel award announced for the 2012 GSA Yeast Genetics and Molecular Biology Meeting
11. Highlighting molecular clues to the link between childhood maltreatment and later suicide
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/6/2017)... BOULDER, Colo. , Jan. 5, 2017 /PRNewswire/ ... join the "Digital Life Alliance" established by iCarbonX, ... in 2015 to build a "Global Digital Health ... based on a combination of individual,s biological, behavioral ... Under the agreement between the companies, SomaLogic will ...
(Date:12/22/2016)... Dec. 20, 2016  As part of its longstanding mission ... personal genetics company, recently released its latest children,s book, titled ... book focuses on the topics of inheritance and variation of ... (NGSS) taught in elementary school classrooms in the US. ... by illustrator Ariana Killoran , whose previous book with ...
(Date:12/16/2016)... Dec. 16, 2016   IdentyTechSolutions America LLC ... products and solutions and a cutting-edge manufacturer of ... it is offering seamless, integrated solutions that comprise ... products. The solutions provide IdentyTech,s customers with combined ... facilities from crime and theft. "We ...
Breaking Biology News(10 mins):
(Date:1/19/2017)... and HOUSTON , Jan. 19, ... today announced the formation of its Medical/Clinical Advisory ... and industry veterans who enhance the range and ... accelerates development of its novel prenatal diagnostic tests.  ... clinical and strategic guidance for the company,s product ...
(Date:1/19/2017)... 19, 2017 Research and Markets ... has announced the addition of the ... Forecast to 2025" report to their offering. ... The report provides a detailed analysis on current and future market trends ... using estimated market values as the base numbers Key ...
(Date:1/19/2017)... ... January 19, 2017 , ... November Research Group, ... biopharmaceutical and medical device manufacturers and regulators, is proud to announce the worldwide ... email client designed to provide product vigilance departments with the flexibility and ease ...
(Date:1/19/2017)... , Jan. 19, 2017  ArmaGen, Inc., today ... , Ph.D., as chief executive officer, as well ... Dr. Schmidt brings to ArmaGen more than 17 years ... and development of biotherapeutics and pharmaceuticals. ... the diverse experience and skillset necessary to lead ...
Breaking Biology Technology: