Figure 3. Interplay between RNA Pol-II and co-transcriptional R-loop.
(A) The impairment of transcriptional elongation causes RNA Pol-II pausing and promotes R-loop accumulation. Depletion of BRCA1 in cancer induces Pol-II pausing and triggers excessive R-loop formation, partly through the enhanced NELFB/COBRA1 activity. Along with TFIIS, BRD4 and BRD2 recruit pTEFb and TOP1, respectively, to facilitate transcriptional elongation. A transcriptional-elongation-defective mutant of TFIIS stimulates anterior R-loop formation.
(B) Crosstalk among R-loops, Pol-II-mediated antisense transcription and various R-loop structure “sensors” such as ssDNA-specific binder and R-loop (RNA-DNA hybrid) “readers” is crucial for metabolism of R-loop and R-loop-related gene regulation. In the mammalian cells, accumulated R-loops promote antisense transcription of lncRNAs near the TSS of lncRNAs.