GSE108125
Transcriptome-wide map of SRSF9 bining in the presence and absence of ADAR2 in HEK293T cells
Here, we show that the splicing factor SRSF9 selectively controls the editing of many brain-specific sites in mammals. SRSF9 is more lowly expressed in the mammalian brain than in non-brain tissues. Gene perturbation experiments and minigene analysis of candidate sites demonstrated that SRSF9 could robustly repress A-to-I editing by ADAR2. We found that SRSF9 biochemically interacted with ADAR2 in the nucleus via its RRM2 domain alone. Additionally, this interaction required the presence of the RNA substrate and disrupted the formation of ADAR2 dimers. Using transcriptome-wide location analysis and genome-wide RNA profiling, we identified 1,328 editing sites that are regulated directly by SRSF9. Importantly, we showed that this SRSF9 regulon is significantly enriched for brain-specific editing sites despite our unbiased approach. We further provide evidence that SRSF9 prevents cells from undergoing apoptosis possibly through the inhibition of ADAR2-mediated editing. Collectively, our results highlighted the importance of SRSF9 as an editing regulator and suggested that other splicing factors may also be involved in regulating RNA editing. Overall design: Elucidting the repressive action of SRSF9 on the ADAR2 targets