Expanding RNA editing toolkit using an IDR-based strategy

doi:10.1016/j.omtn.2024.102190

	Expanding RNA editing toolkit using an IDR-based strategy
	Di MH(邸明慧)1,2 ; Lv JJ(吕君君)1,2 ; Jing ZY(荆征宇)1,2 ; Yang YJ(杨艺杰)1 ; Yan KL(闫昆仑)1 ; Wu JG(吴建国)1,2 ; Ge JY(葛剑洋)1,2 ; Simone Rauch 3; Bryan Dickinson 3; Chi T(池天)1,4
	2024-06
发表期刊	MOLECULAR THERAPY - NUCLEIC ACIDS (IF:6.5[JCR-2023],6.7[5-Year])
ISSN	2162-2531
卷号	35 期号:2
发表状态	已发表
DOI	10.1016/j.omtn.2024.102190
摘要	RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short histidine-rich domain (HRD), which is derived from the internal disordered region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C > U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C > U RNA base editors.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Science Foundation of China[92068115] ; National Institute of General Medical Sciences of the National Institutes of Health NIH[R35 GM119840]
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:001237142900001
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/366072
专题	生命科学与技术学院生命科学与技术学院_PI研究组_池天组生命科学与技术学院_硕士生生命科学与技术学院_博士生
共同第一作者	Wu JG(吴建国); Chi T(池天)
通讯作者	Bryan Dickinson; Chi T(池天)
作者单位	1.School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China 2.Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031; University of Chinese Academy of Sciences, China 3.Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States 4.Department of Immunobiology, Yale University Medical School, New Haven, CT, USA
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Di MH,Lv JJ,Jing ZY,et al. Expanding RNA editing toolkit using an IDR-based strategy[J]. MOLECULAR THERAPY - NUCLEIC ACIDS,2024,35(2).
APA	Di MH.,Lv JJ.,Jing ZY.,Yang YJ.,Yan KL.,...&Chi T.(2024).Expanding RNA editing toolkit using an IDR-based strategy.MOLECULAR THERAPY - NUCLEIC ACIDS,35(2).
MLA	Di MH,et al."Expanding RNA editing toolkit using an IDR-based strategy".MOLECULAR THERAPY - NUCLEIC ACIDS 35.2(2024).