Knockout of circRNAs by base editing back-splice sites of circularized exons

Many circular RNAs (circRNAs) are produced from back-splicing of exons of precursor mRNAs and are generally co-expressed with cognate linear RNAs. Methods for circRNA-specific knockout are lacking, largely due to sequence overlaps between forms. Here, we use base editors (BEs) for circRNA depletion....

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Published inGenome Biology Vol. 23; no. 1; p. 16
Main Authors Gao, Xiang, Ma, Xu-Kai, Li, Xiang, Li, Guo-Wei, Liu, Chu-Xiao, Zhang, Jun, Wang, Ying, Wei, Jia, Chen, Jia, Chen, Ling-Ling, Yang, Li
Format Journal Article
LanguageEnglish
Published England BioMed Central 10.01.2022
BMC
Subjects
Back-splicing
Base editor
Biosynthesis
Circular RNA
CRISPR
DNA methylation
Exons
Gene loci
Genomes
Knockout
Method
Predominantly back-spliced exon
RNA - genetics
RNA Precursors
RNA Splicing
RNA, Circular
Splicing
Circular RNA
Back-splicing
Splicing
Base editor
Knockout
Predominantly back-spliced exon
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Summary:Many circular RNAs (circRNAs) are produced from back-splicing of exons of precursor mRNAs and are generally co-expressed with cognate linear RNAs. Methods for circRNA-specific knockout are lacking, largely due to sequence overlaps between forms. Here, we use base editors (BEs) for circRNA depletion. By targeting splice sites involved in both back-splicing and canonical splicing, BEs can repress circular and linear RNAs. Targeting sites predominantly for circRNA biogenesis, BEs could efficiently repress the production of circular but not linear RNAs. As hundreds of exons are predominantly back-spliced to produce circRNAs, this provides an efficient method to deplete circRNAs for functional study.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-021-02563-0