气候变化领域集成服务门户(CCPortal): Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration

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DOI	10.1073/pnas.2022751118
	Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration
	Fukuda S.; Varshney A.; Fowler B.J.; Wang S.-B.; Narendran S.; Ambati K.; Yasuma T.; Magagnoli J.; Leung H.; Hirahara S.; Nagasaka Y.; Yasuma R.; Apicella I.; Pereira F.; Makin R.D.; Magner E.; Liu X.; Sun J.; Wang M.; Baker K.; Marion K.M.; Huang X.; Baghdasaryan E.; Ambati M.; Ambati V.L.; Pandey A.; Pandya L.; Cummings T.; Banerjee D.; Huang P.; Yerramothu P.; Tolstonog G.V.; Held U.; Erwin J.A.; Paquola A.C.M.; Herdy J.R.; Ogura Y.; Terasaki H.; Oshika T.; Darwish S.; Singh R.K.; Mozaffari S.; Bhattarai D.; Kim K.B.; Hardin J.W.; Bennett C.L.; Hinton D.R.; Hanson T.E.; Röver C.; Parang K.; Kerur N.; Liu J.; Werner B.C.; Scott Sutton S.; Sadda S.R.; Schumann G.G.; Gelfand B.D.; Gage F.H.; Ambati J.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	Alu retroelements propagate via retrotransposition by hijacking long interspersed nuclear element-1 (L1) reverse transcriptase (RT) and endonuclease activities. Reverse transcription of Alu RNA into complementary DNA (cDNA) is presumed to occur exclusively in the nucleus at the genomic integration site. Whether Alu cDNA is synthesized independently of genomic integration is unknown. Alu RNA promotes retinal pigmented epithelium (RPE) death in geographic atrophy, an untreatable type of age-related macular degeneration. We report that Alu RNA-induced RPE degeneration is mediated via cytoplasmic L1-reverse-transcribed Alu cDNA independently of retrotransposition. Alu RNA did not induce cDNA production or RPE degeneration in L1-inhibited animals or human cells. Alu reverse transcription can be initiated in the cytoplasm via self-priming of Alu RNA. In four health insurance databases, use of nucleoside RT inhibitors was associated with reduced risk of developing atrophic macular degeneration (pooled adjusted hazard ratio, 0.616; 95% confidence interval, 0.493-0.770), thus identifying inhibitors of this Alu replication cycle shunt as potential therapies for a major cause of blindness. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Alu; Health insurance databases; Macular degeneration; Retina; Retrotransposon
语种	英语
scopus关键词	Alu complementary DNA; Alu RNA; complementary DNA; nucleic acid; unclassified drug; adult; age related macular degeneration; animal cell; animal experiment; animal model; Article; blindness; cell death; controlled study; cytoplasm; disease course; DNA probe; DNA replication; enzyme inhibition; human; human cell; nonhuman; nucleic acid synthesis; priority journal; retinal pigment epithelium; reverse transcription; risk factor; RNA probe; RNA replication
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180767
作者单位	Center for Advanced Vision Science, School of Medicine, University of Virginia, Charlottesville, VA 22908, United States; Department of Ophthalmology, School of Medicine, University of Virginia, Charlottesville, VA 22908, United States; Department of Ophthalmology, University of Tsukuba, Ibaraki, 305-8575, Japan; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, United States; Aravind Eye Hospital System, Madurai, 625020, India; Department of Ophthalmology, Graduate School of Medicine, Nagoya University, Nagoya, 464-8601, Japan; Dorn Research Institute, Columbia Veterans Affairs Health Care System, Columbia, SC 29209, United States; Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, United States; Department of Ophthalmology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan; Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medici...
推荐引用方式 GB/T 7714	Fukuda S.,Varshney A.,Fowler B.J.,et al. Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration[J],2021,118(6).
APA	Fukuda S..,Varshney A..,Fowler B.J..,Wang S.-B..,Narendran S..,...&Ambati J..(2021).Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Fukuda S.,et al."Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).