ARID1A loss promotes RNA editing of CDK13 in an ADAR1-dependent manner
Tianyu Zhu,
Qian Li,
Zhe Zhang,
Jiahao Shi,
Yongyun Li,
Feng Zhang,
Lingjie Li,
Xin Song,
Jianfeng Shen,
Renbing Jia
Affiliations
Tianyu Zhu
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Qian Li
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Zhe Zhang
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Jiahao Shi
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Yongyun Li
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Feng Zhang
Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine
Lingjie Li
Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine
Xin Song
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Jianfeng Shen
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Renbing Jia
Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Abstract Background ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear. Results Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment. Conclusions ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.
