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:4/28/2016)... Sweden , April 28, 2016 First ... M (139.9), up 966% compared with the first quarter of 2015 ... profit totaled SEK 589.1 M (loss: 18.8) and the operating margin ... 7.12 (loss: 0.32) Cash flow from operations was SEK ... The 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. ...
(Date:4/15/2016)...  A new partnership announced today will help ... in a fraction of the time it takes ... life insurance policies to consumers without requiring inconvenient ... Diagnostics, rapid testing (A1C, Cotinine and HIV) and ... weight, pulse, BMI, and activity data) available at ...
(Date:3/31/2016)... March 31, 2016   ... or the "Company") LegacyXChange is excited to ... its soon to be launched online site for trading ... ) will also provide potential shareholders a sense ... technology to an industry that is notorious for fraud. ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... and San Diego, CA (PRWEB) , ... April 29, 2016 , ... ... Stem Cell Foundation (NSCF) to support the development of a patient-specific stem cell therapy ... Andrés Bratt-Leal in the lab of Dr. Jeanne Loring at The Scripps Research Institute ...
(Date:4/28/2016)... 2016 Q BioMed Inc. ... CEO  was featured in an article he wrote ... Fear To Tread: http://www.lifescienceleader.com/doc/accelerators-enter-when-vcs-fear-to-tread-0001 ... is an essential business journal for life science ... to Big Pharmas. Their content is designed to ...
(Date:4/28/2016)... Windsor, Connecticut (PRWEB) , ... April 28, 2016 ... ... Morris Group, Inc., will hold an open house for regional manufacturers at its ... and displays from Tsugami, Okuma, Hardinge Group, Chiron and Trumpf. Almost 20 ...
(Date:4/27/2016)... ... April 27, 2016 , ... Most consumers engage with biometrics ... for secure access, voice recognition for hands-free communication, and facial recognition to help ... biometrics technology today. But if they asked Joey Pritikin, Vice President of ...
Breaking Biology Technology: