Illumina bead array -/+ UV ASCC3 long isoform shRNA knockdown cells

The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage

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Williamson L, Saponaro M, Boeing S, East P, Mitter R, Kantidakis T, Kelly GP, Lobley A, Walker J, Spencer-Dene B, Howell M, Stewart A, Svejstrup JQ