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Suppression of adenosine-to-inosine (A-to-I) RNA editome by death associated protein 3 (DAP3) promotes cancer progression

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, the...

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Detalles Bibliográficos
Autores principales: Han, Jian, An, Omer, Hong, HuiQi, Chan, Tim Hon Man, Song, Yangyang, Shen, Haoqing, Tang, Sze Jing, Lin, Jaymie Siqi, Ng, Vanessa Hui En, Tay, Daryl Jin Tai, Molias, Fernando Bellido, Pitcheshwar, Priyankaa, Tan, Hui Qing, Yang, Henry, Chen, Leilei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299630/
https://www.ncbi.nlm.nih.gov/pubmed/32596459
http://dx.doi.org/10.1126/sciadv.aba5136
Descripción
Sumario: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 PDZD7(WT), which is more tumorigenic than edited PDZD7(Stop518W), is accumulated in tumors. In sum, cancer cells may acquire malignant properties for their survival advantage through suppressing RNA editome by DAP3.