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:4/24/2017)... 2017 Janice Kephart , former ... Strategy Partners, LLP (IdSP) , today issues the ... Trump,s March 6, 2017 Executive Order: Protecting ... can be instilled with greater confidence, enabling the ... refugee applications are suspended by until at least ...
(Date:4/18/2017)...  Socionext Inc., a global expert in SoC-based imaging and computing ... M820, which features the company,s hybrid codec technology. A demonstration utilizing ... Inc., will be showcased during the upcoming Medtec Japan at Tokyo ... Las Vegas Convention Center April 24-27. ... Click here for an image ...
(Date:4/13/2017)... UBM,s Advanced Design and Manufacturing event in ... and evolving technology through its 3D Printing and Smart ... the expo portion of the event and feature a ... on trending topics within 3D printing and smart manufacturing. ... will take place June 13-15, 2017 at the Jacob K. ...
Breaking Biology News(10 mins):
(Date:8/15/2017)... , ... August 15, 2017 , ... Kapstone Medical ... 10 years of successes helping medical technology companies and inventors develop and safeguard their ... renowned full-service national engineering firm with a portfolio of clients in the United States ...
(Date:8/15/2017)... ... August 15, 2017 , ... ... of 6” modular downlights designed to stay tightly sealed and perform efficiently for ... damp and wet location listings just aren't enough, such as: hospitals; behavioral health ...
(Date:8/14/2017)... ... August 14, 2017 , ... ... antibodies. Key researchers in the antibody community have recently come together to address ... antibodies in the laboratory. , The team at Thermo Fisher ...
(Date:8/11/2017)... ... August 11, 2017 , ... A staple in the community for more ... incorporate important key elements including a new digital marketing strategy and updated logo. , ... Bill Miller has partnered with the South Texas Blood & Tissue Center for the ...
Breaking Biology Technology: