Highly-conserved lncRNAs regulates the BRCA1 locus under broad-stress responses [PRO-seq]

RNA polymerase II inhibition triggers a cellular stress response that paradoxically leads to the overexpression of certain transcripts. To investigate the underlying mechanism, we conducted genome-wide assays in human cells treated with triptolide, which disrupts the translocase/DNA helicase activity of XPB, part of TFIIH. Our analysis revealed that XPB activity-independent transcription of genes originate from thermodynamically unstable promoters. Among the upregulated genes, we identified three novel regulatory lncRNAs—TILR-1, TILR-2, and LINC00910 that are highly conserved among primates. Their expression is interdependent, and together, they regulate the nearby BRCA1 locus transcription. We observed that this network of transcripts is also activated in other stress responses, like heat shock and arsenic. We suggest that the BRCA1 locus and its lncRNAs regulators are part of a transcriptional switch that respond to broad stress conditions. Overall design: PRO-seq in K562 cells treated with different triptolide concentrations or DMSO