Group: Jantsch, Michael

Research Focus

Functional consequences of RNA editing

Eukaryotic RNAs can be post-transcriptionally capped, spliced, polyadenylated, edited, and chemically modified. These processing events determine fate and function of RNAs. Today, more than 100 different types of RNA-modifications are known. Yet, the machineries that add these modifications, the factors that bind and recognise them, and their biological consequences are poorly understood.
Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in structured regions of RNAs. Inosines basepair with cytosines and therefore ADAR-mediated RNA-editing can recode RNAs, and change the folding and fate of RNAs. More than a million ADAR editing sites are known in the human transcriptome which are introduced by the two active enzymes ADAR1 or ADAR2. Mice lacking either ADAR1 or ADAR2 die prematurely and mutations in human ADARs are associated with Aicardi Goutières syndrome and dyschromatosis symmetrica hereditaria, depending on the enzyme affected. Yet, the consequences of ADAR-mediated RNA editing and its role in cellular and organismic function are poorly understood.

Main objectives

We aim at understanding the consequences of ADAR-mediated RNA editing at the cellular and organismic level. Specifically, we focus on an RNA editing event that leads to an amino acid exchanges in the actin-cross-linking protein filamin A (FLNA).
We also study why lack of ADAR1-mediated editing leads to elevated interferon signalling. Lastly, we study the interplay of RNA-editing with other RNA-processing events.

Content of research

We use transgenic mice, cell biological tools, and transcriptome analyses to study the consequences of RNA-editing events. Using mice deficient in either of the two RNA-editing enzymes ADAR1 or ADAR2 we study the interplay of these two enzymes with other RNA processing machineries. A mouse model specifically defective in filamin A pre-mRNA editing is used to study the consequences of this highly conserved RNA-editing event.