RNA-editing by adenosine deaminases acting on RNA (ADARs) leads to the post-transcriptional conversion of adenosines to inosines. As inosines are interpreted as guanosines by most cellular processes this type of editing can affect the coding potential of an RNA, its folding, stablility, or localization. ADAR mediated editing is widespread in metazoa and affects thousands of transcripts in the human transcriptome. Together with alternative splicing, RNA-editing therefore leads to massive diversification of the proteome. This is exemplified best by the fact that both RNA-editing, and alternative splicing are most abundant in the mammalian brain. Consistent with its important function in modulating the transcriptome, RNA editing is essential for normal life and development in many organisms. Our research is focused on topics related to this type of RNA editing and aims at understanding the biochemical, cellular, and organismic consequences of A to I conversion.

Editing in protein coding mRNAs

A handful of highly conserved protein coding targets for A to I editing are known today. To understand the impact of editing on these RNAs and their encoded proteins we are generating transgenic mice that are impaired in specific editing events. Our studies show that lack of editing of the mRNAs encoding the actin crosslinking protein filamin A leads to behavioral defects disturbed neuronal outgrowth underscoring the importance of editing for proper neuronal function.

Repetitive elements as modulators of gene expression

Massive editing can be found in highly structured 3’ ends of mRNAs. These editing sites are localized in basepaired regions formed between inverted repetitive elements of the SINE family. Analysis of these untranslated regions in reporter gene assays demonstrates that inverted SINES lead to a dramatic reduction in gene expression. Interestingly, despite being a target for A to I editing, this phenomenon is not depending on editing activity but is triggered by the double stranded structure formed in the 3’ UTR. Deciphering the mechanisms by which these 3’ ends control gene expression is another research goal of our group.