Targeted RNA N6‐Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells
| Autor: | Jia Wang, Weisheng Cheng, Yu-Li Zhao, Qingquan Zhao, Nan Cao, Zhiju Zhao, Xuena Chen, Guan-Zheng Luo, Guo-Shi Chai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
General Chemical Engineering
Science General Physics and Astronomy Medicine (miscellaneous) 02 engineering and technology Cell fate determination 010402 general chemistry 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) SOX2 General Materials Science Induced pluripotent stem cell Chemistry Cell growth Methyltransferase complex General Engineering RNA differentiation 021001 nanoscience & nanotechnology ALKBH5 Embryonic stem cell 0104 chemical sciences Cell biology Cell Fate Control CRISPR embryonic structures m6A RNA modification biological phenomena cell phenomena and immunity pluripotent stem cells 0210 nano-technology |
| Zdroj: | Advanced Science, Vol 8, Iss 11, Pp n/a-n/a (2021) |
| ISSN: | 2198-3844 |
| Popis: | Deficiency of the N6 -methyladenosine (m6 A) methyltransferase complex results in global reduction of m6 A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m6 A methylation affects cell fate decisions due to the inability to modulate individual m6 A modification in ESCs with precise temporal control. Here, a targeted RNA m6 A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m6 A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m6 A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m6 A modification in hESCs, enabling cell fate control studies at the epitranscriptional level. |
| Databáze: | OpenAIRE |
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