Figure 1. Spliceosome mutations confer an R loop-dependent vulnerability.

MDS-associated spliceosome mutants induce alternative RNA splicing, which may contribute to MDS pathogenesis. The spliceosome mutants also induce R-loops, possibly owing to the stalling of RNA polymerase II. Whether and how R-loops contribute to MDS pathogenesis is still unknown. Nonetheless, R-loops trigger an ATR response and render cells dependent on ATR for survival.