Open AccessTRADES: Targeted RNA Demethylation by SunTag System
Author(s) -
Mo Jing,
Chen Zonggui,
Qin Shanshan,
Li Shu,
Liu Chuangang,
Zhang Lu,
Ran Ruoxi,
Kong Ying,
Wang Fang,
Liu Songmei,
Zhou Yu,
Zhang Xiaolian,
Weng Xiaocheng,
Zhou Xiang
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202001402
Subject(s) - demethylation , rna , messenger rna , demethylase , biology , computational biology , rna interference , methylation , hela , microbiology and biotechnology , gene , gene expression , genetics , dna methylation , cell , epigenetics
N6‐methyladenosine (m 6 A) is rapidly being studied and uncovered to play a significant role in various biological processes as well as in RNA fate and functions, while the effects of defined m 6 A sites are rarely characterized for the lack of convenient tools. To provide an applicable method to remove m 6 A modification at specific loci, an m 6 A editing system called “ t argeted R N A de methylation by S unTag system (TRADES)” is engineered. In this system, the targeting element dCas13b is fused to ten copies of GCN4 peptides which can recruit multiple scFv‐fusion RNA demethylase to demethylate the target m 6 A site. Owing to this design, TRADES is more flexible to the indistinct m 6 A sites for its wide editing window. By site‐specific demethylation of messenger RNA (mRNA) SON A2699, the lifetime of SON RNA is successfully prolonged in HeLa cells. Meanwhile, TRADES negligibly influences the lifetime of other non‐targeted transcripts. TRADES also can regulate the gene expression of target transcript in an m 6 A‐dependent manner. Moreover, the interference occuring for HBV and HIV replications demonstrates that the TRADES system holds potential in viral life cycle regulation and clinical applications.