Filamin RNA-editing controls cellular and organ integrity

Filamins are cellular proteins that cross-link the actin cytoskeleton and thus regulate the shape and stiffness of cells. In addition, filamins interact with transmembrane proteins such as receptors and integrins, which in turn interact with proteins of the extracellular matrix. Therefore, filamins not only regulate the shape and stiffness of cells, but also their position in the tissue matrix and can also influence the firmness of surrounding tissues. Three filamins are known in mammals, filamin A, filamin B and filamin C. The functions of individual filamines appear to overlap, although individual filaminss appear to have different importance in specific tissues. Filamins can be modified in different ways. One regulated type of modification takes place before translation, at the level of the messenger RNA. Through so-called RNA-editing, a single adenosine in the coding region of filamin A or filamin B is converted into an inosine. Inosines are translated as guanosines. Therefore, by changing a codon a glutamine is converted into an arginine in the final filamin protein. We have already shown that RNA-editing of filamin A influences the stiffness of cells, the contraction of the vasculature, but also the formation of blood vessels. The present project aims to investigate how RNA editing of filamin A and filamin B affects other tissues. To this end, changes in intracellular signaling pathways will be investigated, as well as the effect of editing individual filamins on the integrity and physiology of tissues and organisms. This should provide information about the involvement of RNA editing of filamines in the development of diseases.