生物
RNA编辑
内含子
RNA剪接
核糖核酸
环状RNA
计算生物学
转录组
遗传学
RNA结合蛋白
基因
基因表达
作者
Haoqing Shen,Ömer An,Xi Ren,Yangyang Song,Sze Jing Tang,Xin-Yu Ke,Jian Han,Daryl Jin Tai Tay,Vanessa Hui En Ng,Fernando Bellido Molias,Priyankaa Pitcheshwar,Ka Wai Leong,Ker‐Kan Tan,Henry Yang
标识
DOI:10.1038/s41467-022-29138-2
摘要
Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis.
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