Mechanism and specific inhibition of Alu-RNA toxicity in AMD

  • Yasuma, Tetsuhiro (PI)

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Geographic atrophy (GA), a form of age-related macular degeneration (AMD), is the major cause of blindness in United States and developed countries and retinal pigment epithelium (RPE) death is the center of (GA) development. Our group has shown Dicer loss and consequent accumulation of Alu-RNAs promote GA. Alu-RNAs are transcribed from Alu-elements that consist more than 10.6% of human genome. We further indicated that inflammation process called NLRP3 inflammasome is involved in RPE death in Alu-RNA toxicity, but the detailed mechanism is not well-known yet. Alu-RNA is derived from 7SL RNA, an indispensable component of signal recognition particle (SRP) that is the key of membrane protein synthesis, and binds to other SRP components. I hypothesize that Alu-RNA disrupts signal recognition particles (SRP). To demonstrate this, we utilize Alu-RNA derivatives with varied affinity to SRPs, supplementation of SRPs and 7SL RNA to relieve Alu toxicity, and RNA interference against Alu-RNA.
Effective start/end date7/1/146/30/15


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