Spatio-temporal profiling of Filamin A RNA-editing reveals ADAR preferences and high editing levels outside neuronal tissues

RNA editing by ADARs can change the coding potential of protein-coding mRNAs. So far, this type of RNA editing has mainly been shown to affect RNAs expressed in the nervous system with much lower editing levels being observed in other tissues. The actin crosslinking proteins filamin α and filamin β are widely expressed in most tissues. The mRNAs encoding either protein are edited at the same position leading to a conserved Q to R exchange in both proteins. Using bar-coded next generation sequencing, we show that editing of filamin α is most abundant in the gastrointestinal tract and only to a lesser extent in the nervous system. Using knockout mice, we show that ADARB1 (ADAR2) is responsible for the majority of FLNA editing, while ADAR1 can edit filamin α mRNA in some tissues quite efficiently. Interestingly, editing levels of filamin α and β do not follow the same trend across tissues, suggesting a substrate-specific regulation of editing.