Comparative functional RNA editomes of neural differentiation from human PSCs

RNA editing is a fundamental mechanism that constitutes the epitranscriptomic complexity. A-to-G editing is the predominant type catalyzed by ADAR1 and ADAR2 in human. Using a CRISPR/Cas9 approach to knockout ADAR1/2, we identified a regulatory role of RNA editing in directed differentiation of human embryonic stem cells (hESCs) toward neural progenitor cells (NPCs). Genome-wide landscapes of A-to-G editing in hESCs and four derivative cell lineages representing all three germ layers and the extraembryonic cell fate were profiled, with a particular focus on neural differentiation. Furthermore, a bioinformatics-guided case study identified a potential functional editing event in ZYG11B 3'UTR that might play a role in regulation of NPC differentiation through gain of miR6089 targeting. Collectively, our study established the functional role of A-to-G RNA editing in neural lineage differentiation; illustrated the RNA editing landscapes of hESCs and NPC differentiation; and shed new light on molecular insights thereof.