Cooperating with Xuena Chen (Zhongshan School of Medicine, Sun Yat-sen University), Qingquan Zhao(Zhongshan School of Medicine, Sun Yat-sen University), Yu-Li Zhao and Guo-Shi have published the paper titled Targeted RNA N6-Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells in Advanced Science. Yu-Li Zhao is a co-first author, and Guo-Shi Chai is the second author. Congratulations!

Deficiency of the N6-methyladenosine (m6A) methyltransferase complex results in global reduction of m6A abundance and defective cell development in embryonic stem cells (ESCs). However, it’s unclear whether regional m6A methylation affects cell fate decisions due to the inability to modulate individual m6A modification in ESCs with precise temporal control. Here, a targeted RNA m6A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs), in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m6A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m6A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs.

By Yuli Zhao.