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The RNAs encoding the actin crosslinking proteins Filamin A and Filamin B are both edited at the same position leading to the conversion of a glutamine (Q) to and arginine (R) codon. Transgenic mice impaired in the editing of Filamin A show elevated contraction of smooth muscle cells and reduced cell migration. We are studying the physiological consequences of the elevated smooth muscle cell contraction and the underlying molecular mechanisms leading to this phenomenon.

ADAR-mediated RNA-editing relies on the presence of double-stranded structures in RNAs. These structures are frequently formed between intronic and exonic sequences. Consequently, the efficiency of splicing will affect the rate of editing. We are therefore testing the consequences of altered RNA-splicing kinetics on RNA editing at a transcriptome-wide level.

ADAR-mediated RNA editing occurs in intronic and exonic sequences and will affect the binding of proteins to RNA. Clearly, altered sequence and protein composition will interfere with other RNA processing events such as RNA-splicing, modification, or RNA export. We are therefore studying the processing and cellular fate of RNAs in the presence or absence of ADARs.