circular RNA Kat6b-e2 expression safeguards self-renewal and lineage differentiation of mouse embryonic stem cells

Circular RNA has been reported to be dynamically expressed during embryonic development and regulates human embryonic stem cells (hESCs), but the identification and regulation of functional circular RNA in mouse embryonic stem cells (mESC) remains unclear. Here we found over 1,000 circular RNAs in different mESC states. One of these, circular RNA Kat6b-exon2 (circKat6b-e2), was significantly overexpressed in mESCs. Furthermore, short-hair RNA (shRNA) mediated knockdown of circKat6b-e2 expression significantly inhibited mESC self-renewal and EB differentiation. The transcriptome also revealed that circKat6b-e2 is required to ensure the differentiation of the mESC lineage. Finally, we also found that more Alu elements surrounding circKat6b-e2 were necessary factors for its expression. Conclusions: our study shows that Alu element-dependent expression of circKat6b-e2 mediates mESC self-renewal and lineage differentiation. Three biological replicates were analyzed for each experimental condition. WT and knockdown cells were RNA-seq in ESCs or EBs-day 6.