library_construction_protocol: Fractionation of cytoplasmic and nuclear RNA was performed using digitonin. cells were washed in ice cold PBS before permeabilised in digitonin solution (50 μg/mL digitonin (MP Biomedicals), 100 mM NaCl, 10 mM Tris, pH 8.0, 40 U/mL RNaseOUT (Invitrogen), 1 x Protease inhibitor cocktail (Roche)) for 15 min on ice. Nuclear and cytoplasmic fractions were separated by centrifugation for 3 min at 1000 g at 4°C. RNA in each fraction was then recovered using RNeasy Mini Kit (Qiagen) according to manufacturer instructions. Samples were treated with RNase H for ribosomal RNA depletion then purified with RNA beads (Axygen Ampure) following the standard bead clean up protocol. Samples were then treated with RNase R for 15 min at 37°C (0.2 μl RNase R and 2μl 10X buffer, Lucigen) to enrich for circRNA, followed by RNA bead purification (Axygen Ampure). Stranded RNA libraries were made using the KAPA RNA HyperPrep Kit (Roche)