DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D; Fowler, Benjamin J; Cho, Won Gil; Kleinman, Mark E; Ponicsan, Steven L; Hauswirth, William W; Chiodo, Vince A; Kariko, Katalin; Provis, Jan; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W; Braun, Robert E; Hinton, David R; Zhang, Qing; Grossniklaus, Hans E; Madigan, Michele C; Milam, Ann H; Justice, Nikki L; Albuquerque, Romulo JC; Blandford, Alexander D; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R; Ambati, Balamurali K; Rudin, Charles M; Chong, Mark MW; Provost, Patrick; Kugel, Jennifer F; Goodrich, James A; Dunaief, Joshua L; Baffi, Judit Z; Ambati, Jayakrishna
Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu...[Show more]
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