UNIVERSITY OF COLOGNE

Kath-Schorr lab - Institute for Organic Chemistry

The Role of Z-RNA in Relocalization of Zα Doman-Containing Proteins in Cells

Certain regions in double stranded (ds) RNA are able to form left-handed duplex structures. This left-handed RNA conformation, termed Z-RNA due to its zig-zag backbone structure, is highly unstable and forms in vitro only at high salt conditions or using stabilizing nucleotide modifications. Due to its unstable character and related challenges in studying Z-RNA formation, only in recent years evidence has emerged that Z-RNA duplexes are transiently formed in cells and have important biological functions, in particular may play a major role in the innate immune response. 

Z-DNA/Z-RNA is bound by the Zα domain protein family that includes in mammals only two proteins, adenosine deaminase acting on RNA 1 (ADAR1) and Z-DNA-binding protein 1 (ZBP1). During cellular stresses such as heat, arsenite and interferon-induced stress, both ADAR1 and ZBP1 relocalize from bulk cytosol to cytosolic stress granules based on the presence of Zα domains. There is strong evidence that this event is associated with Z-RNA formation as mutations in Zα domains preventing dsRNA binding abolish protein relocalization. We aim to investigate the transient formation of Z-RNA and its impact on relocalization of Zα domain proteins upon cellular stress.