Featured Research

from universities, journals, and other organizations

Molecular mechanisms underlying prevention of autoimmunity by Roquin revealed

Date:
July 14, 2014
Source:
Helmholtz Zentrum München - German Research Center for Environmental Health
Summary:
Scientists have moved an important step closer to understanding molecular mechanisms of autoimmune diseases. They solved the three-dimensional structure of the Roquin protein when bound to messenger ribonucleic acid molecules. The results revealed that there is a much wider range of functionally important Roquin binding partners than previously assumed.

Roquin (blue) binding to mRNA (violet).
Credit: Sattler/HMGU

Scientists at the Helmholtz Zentrum München, the Ludwig-Maximilians University of Munich (LMU) and the Technische Universität München (TUM) have moved an important step closer to understanding molecular mechanisms of autoimmune diseases. They solved the three-dimensional structure of the Roquin protein when bound to messenger ribonucleic acid (mRNA) molecules. The results revealed that there is a much wider range of functionally important Roquin binding partners than previously assumed. The novel findings are published in the journal Nature Structural & Molecular Biology.

Related Articles


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 München, Ludwig-Maximilian University (LMU) and the Technische Universität München (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 München 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 München 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.


Story Source:

The above story is based on materials provided by Helmholtz Zentrum München - German Research Center for Environmental Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. Schlundt A. et al. Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. Nat Struct Mol Biol, July 2014 DOI: 10.1038/nsmb.2855

Cite This Page:

Helmholtz Zentrum München - German Research Center for Environmental Health. "Molecular mechanisms underlying prevention of autoimmunity by Roquin revealed." ScienceDaily. ScienceDaily, 14 July 2014. <www.sciencedaily.com/releases/2014/07/140714105927.htm>.
Helmholtz Zentrum München - German Research Center for Environmental Health. (2014, July 14). Molecular mechanisms underlying prevention of autoimmunity by Roquin revealed. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2014/07/140714105927.htm
Helmholtz Zentrum München - German Research Center for Environmental Health. "Molecular mechanisms underlying prevention of autoimmunity by Roquin revealed." ScienceDaily. www.sciencedaily.com/releases/2014/07/140714105927.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) — A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) — Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) — A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. Video provided by Reuters
Powered by NewsLook.com
Hugging It Out Could Help You Ward Off A Cold

Hugging It Out Could Help You Ward Off A Cold

Newsy (Dec. 21, 2014) — Carnegie Mellon researchers found frequent hugs can help people avoid stress-related illnesses. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins