Transcriptome dynamics of CLK dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor

Here we describe a highly selective novel CLK small molecule inhibitor with high specificityto CLK1/CLK2/CLK3 protein isoforms and favourable stability and in vivo activity, called T3. We show that CLK dependent reactions occur in distinct genomic sequencecontexts with sequence-encoded features that are relatively conserved between different epithelial cell types. We also reveal an unexpected role for CLK proteins in suppression of conjoined gene (CG) transcription, implicating CLK in 3' end processing of transcripts.