DRIP-seq reveals REXO4 and RNaseH1 work together to process R-loops in the same genomic region across the genome.

Endonuclease RNaseH1 acts as a common R-loop resolvase to prevent R-loop accumulation genome-widely, whether there is any exonuclease complementing RNaseH1 to more efficiently resolve R-loops is worth investigation. Here we identify an exonuclease REXO4, which collaborates with RNaseH1 to efficiently degrade R-loops in an “endo- and exo-cleavage coupling” manner.DNA-RNA immunoprecipitation followed by sequencing (DRIP-seq) shows that R-loop regions regulated by REXO4 highly overlap with those regulated by RNaseH1. Overall design: To investigate whether REXO4 and RNaseH1 work together to process R-loops in the same genomic region, we performed DRIP-seq after knocking down REXO4 and RNaseH1 using siRNA in U2OS cells.