RNA editing mediates the functional switch of COPA in a novel mechanism of hepatocarcinogenesis.

Journal of Hepatology
Yangyang SongLeilei Chen

Abstract

RNA editing introduces nucleotide changes in RNA sequences. Recent studies have reported that aberrant adenosine-to-inosine RNA editing is implicated in cancers. Until now, very few functionally important protein-recoding editing targets have been discovered. Here, we investigated the role of a recently discovered protein-recoding editing target COPA (coatomer subunit α) in hepatocellular carcinoma (HCC). Clinical implication of COPA editing was studied in a cohort of 125 HCC patients. CRISPR/Cas9-mediated knockout of the editing site complementary sequence (ECS) was used to delete edited COPA transcripts endogenously. COPA editing-mediated change in its transcript or protein stability was investigated upon actinomycin D or cycloheximide treatment, respectively. Functional difference in tumourigenesis between wild-type and edited COPA (COPAWTvs. COPAI164V) and the exact mechanisms were also studied in cell models and mice. ADAR2 binds to double-stranded RNA formed between edited exon 6 and the ECS at intron 6 of COPA pre-mRNA, causing an isoleucine-to-valine substitution at residue 164. Reduced editing of COPA is implicated in the pathogenesis of HCC, and more importantly, it may be involved in many cancer types. Upon editing, ...Continue Reading

Citations

Feb 18, 2021·RNA Biology·Małgorzata KurkowiakNatalia Marek-Trzonkowska
Apr 8, 2021·BioMed Research International·Jiayao ZhangJun Liu
Apr 10, 2021·International Journal of Biological Macromolecules·Guanghui Ren, Guorong Li
May 12, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daryl Jin Tai TayLeilei Chen

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