Depicting the function of Regnase-3, a new posttranscriptional regulator, in immune responses

• Applicant: Elke Glasmacher, Ph.D.
• Subject Area: Immunology ; Cell Biology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286205495

Our laboratory is interested in mechanisms of gene regulation in immune cells. We found that Regnase-3, a so far undescribed posttranscriptional regulator, plays an important role in immune responses. We want to understand the mechanism of Regnase-3-mediated gene regulation and for which type of immune response Regnase-3 is essential. We have Regnase-3 deficient mice that seem to be impaired in their immune defense and plan to challenge these mice with various infections and other autoimmune triggers to clearly depict for which type of response Regnase-3 is important. Additionally, we would like to identify the cell type and cellular response in which Regnase-3 functions and which targets Regnase-3 regulates. Its family member Regnase-1 is an RNase and we believe that the same holds true for Regnase-3, since the RNase domain and the adjacent Zinc finger are to 99% conserved and we can demonstrate localization to P bodies, foci in the cytoplasm in which RNA silencing takes place. We would like to perform a comparative genome-wide approach using RNA-Sequencing with Regnase-3 wild type and Regnase-3 deficient cells with various stimuli to hypothesize targets that are then verified in reporter assays. Additionally we would like to perform immune-precipitation experiments for Regnase- family members to identify the interaction partners that might facilitate target specificity in cells to ultimately clearly depict the mechanism of Regnase-3 mediated gene regulation.

• DFG Programme: Research Grants