 Hello, my name is Tilman Bergstelmer and I'm Adriana Goncalves. We are here at SEM, the Center for Molecular Medicine of the Austrian Academy of Sciences. Today we will present you our recent paper published in Human Mutation entitled SEMHG1 is a nucleic acid binding protein that is mislocalized due to a cardiac uteri syndrome associated mutations. Before we get started, let us introduce you to the approach that we take in Julio Soperte-Furgus Laboratory at SEM. In Julio's lab we are generally interested in the innate immune system. In order to identify sensors that detect the presence of foreign nucleic acids in the cytosol, we immobilize generic nucleic acids, incubate them with cell extracts and analyze interacting proteins by a protein mass spectrometry approach. One of the proteins we came across was SEMHG1. What was so peculiar about SEMHG1? SEMHG1 caught our attention because mutations in SEMHG1 have been associated with an autoimmune disease called a cardiac uteri syndrome. In order to study this protein in more detail, we teamed up with Jani Crow from the University of Manchester, who is a world expert on a cardiac uteri syndrome. First, we confirmed that SEMHG1 could indeed bind to generic nucleic acids. The link between SEMHG1 and nucleic acids was of particular interest because all other mutations that have been found associated with a cardiac uteri syndrome so far occur in nucleic acid metabolizing enzymes. But in contrast to those enzymes, SEMHG1 did not have any detectable DNAs or RNAs activity. Next, we mapped the nucleic acid binding domain of SEMHG1. We found that mutants lacking the HD domain, but not the SEM domain, were no longer able to associate with nucleic acids. This indicates that nucleic acid binding of SEMHG1 occurs via the HD domain. Then we looked at a large panel of SEMHG1 mutants, all of which were isolated from a cardiac uteri syndrome patients. We used those mutants to study their subcellular localization. Normally, SEMHG1 is exclusively localized in the nucleus. However, in the context of disease, SEMHG1 relocalizes to the cytosol. Because we observed this phenotype for the majority of SEMHG1 mutants we studied, we proposed that mislocalization of SEMHG1 is the major mechanism underlying SEMHG1-driven a cardiac uteri syndrome. We hope you liked the paper and feel free to contact us in case you have any questions or feedback.