Silencing of disease-related genes by small interfering RNAs.
In recent years a new mechanism of posttranscriptional gene silencing has been discovered and named RNA interference. The interference is based on mRNA degradation mediated by small double-stranded RNA molecules approximately 21 nucleotides in length, the so-called short interfering or siRNAs. These molecules are produced from long dsRNAs by Dicer, a dsRNA-specific endonuclease, and cause specific degradation of their mRNA-targets by Watson-Crick base-pairing within a 300 kD multi-enzyme complex named RISC. RNAi is highly conserved between plants and animals of various phyla including mammals. The high sequence-specificity of RNAi makes it a new, promising tool in gene-function analysis as well as in potential therapeutics. In this review the discovery and molecular background of RNAi are summarized and possible fields of application pointed out.
Fuchs
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U
Pediatric Hematology & Oncology, Children's University Hospital Giessen, Feulgenstrasse 12, 35392 Giessen, Germany.
Damm-Welk
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C
Borkhardt
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A
D000818:Animals; D003141:Communicable Diseases / Q000235:genetics / Q000628:therapy; D053487:DEAD-box RNA Helicases; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000628:therapy; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D043244:Ribonuclease III
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004722:Endoribonucleases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases