Journal Article

ADARs act as potent regulators of circular transcriptome in cancer

Leong, Ka Wai, Shen, Haoqing, Yang, Henry, Pitcheshwar, Priyankaa, Han, Jian, Ng, Vanessa Hui En, Molias, Fernando Bellido, Chen, Leilei, Song, Yangyang, Tay, Daryl Jin Tai, Ke, Xin-Yu, An, Omer, Ren, Xi, Tan, Ker-Kan, Tang, Sze Jing

2022

Overview

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. RNA editing and circRNAs are involved in tumorigenesis. Here the authors report that ADARs regulate the circular transcriptome in a bidirectional manner through and beyond their editing function in multiple cancer cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 45/29 / 45/77 / 45/90 / 631/337/1645/1792 / 631/337/1645/1944 / 631/67 / 96/109 / 96/44 / Adenosine / Adenosine - metabolism / Adenosine Deaminase - genetics / Binding / Cancer / Crosstalk / Editing / Heterogeneous-Nuclear Ribonucleoproteins - metabolism / Humanities and Social Sciences / Humans / Introns / multidisciplinary / Neoplasms - genetics / Neoplasms - metabolism / Polypyrimidine Tract-Binding Protein - genetics / RNA Editing / RNA processing / RNA, Circular - genetics / RNA, Double-Stranded / RNA-binding protein / Science / Science (multidisciplinary) / Splicing / Transcriptome / Transcriptomes / Tumorigenesis