HomeLatest HappeningsSuppression of Adenosine-To-Inosine (A-to-I) RNA Editome by Death Associated Protein 3 (DAP3) Promotes Cancer Progression. (Sci Adv, Jun 2020)
Suppression of Adenosine-To-Inosine (A-to-I) RNA Editome by Death Associated Protein 3 (DAP3) Promotes Cancer Progression. (Sci Adv, Jun 2020)
Jian Han1, Omer An1, HuiQi Hong12, Tim Hon Man Chan1, Yangyang Song1, Haoqing Shen1, Sze Jing Tang1, Jaymie Siqi Lin1, Vanessa Hui En Ng1, Daryl Jin Tai Tay1, Fernando Bellido Molias1, Priyankaa Pitcheshwar1, Hui Qing Tan2, Henry Yang1, Leilei Chen13
1Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore. 2Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117549, Singapore. 3Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
RNA editing introduces nucleotide changes in RNA sequences. Recent studies have reported that aberrant A-to-I RNA editing profiles are implicated in cancers. Albeit changes in expression and activity of ADAR genes are thought to have been responsible for the dysregulated RNA editome in diseases, they are not always correlated, indicating the involvement of secondary regulators. Here, we uncover DAP3 as a potent repressor of editing and a strong oncogene in cancer. DAP3 mainly interacts with the deaminase domain of ADAR2 and represses editing via disrupting association of ADAR2 with its target transcripts. PDZD7, an exemplary DAP3-repressed editing target, undergoes a protein recoding editing at stop codon [Stop ?Trp (W)]. Because of editing suppression by DAP3, the unedited PDZD7WT, which is more tumorigenic than edited PDZD7Stop518W, is accumulated in tumors. In sum, cancer cells may acquire malignant properties for their survival advantage through suppressing RNA editome by DAP3.