作者
Hiroki Kaneko, Sami Dridi, Valeria Tarallo, Bradley D Gelfand, Benjamin J Fowler, Won Gil Cho, Mark E Kleinman, Steven L Ponicsan, William W Hauswirth, Vince A Chiodo, Katalin Karikó, Jae Wook Yoo, Dong-ki Lee, Majda Hadziahmetovic, Ying Song, Smita Misra, Gautam Chaudhuri, Frank W Buaas, Robert E Braun, David R Hinton, Qing Zhang, Hans E Grossniklaus, Jan M Provis, Michele C Madigan, Ann H Milam, Nikki L Justice, Romulo JC Albuquerque, Alexander D Blandford, Sasha Bogdanovich, Yoshio Hirano, Jassir Witta, Elaine Fuchs, Dan R Littman, Balamurali K Ambati, Charles M Rudin, Mark MW Chong, Patrick Provost, Jennifer F Kugel, James A Goodrich, Joshua L Dunaief, Judit Z Baffi, Jayakrishna Ambati
发表日期
2011/3/17
期刊
Nature
卷号
471
期号
7338
页码范围
325-330
出版商
Nature Publishing Group UK
简介
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 RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These …
学术搜索中的文章
H Kaneko, S Dridi, V Tarallo, BD Gelfand, BJ Fowler… - Nature, 2011