The RNAi pathway initiated by Dicer-2 in Drosophila.
Injection or expression of double-stranded RNA (dsRNA) in Drosophila serves as a trigger that causes cells to specifically cleave homologous mRNA transcripts. Our approach is to identify essential components of the RNA interference (RNAi) mechanism by isolating and characterizing mutations that cause the RNAi response to be abnormal. These studies have thus far led to the identification of seven genetic loci that encode proteins acting at various steps in the RNAi process. We have molecularly identified several of these proteins. Two are members of the Dicer family. Dicer-1 and Dicer-2 are required for short interfering RNA (siRNA)-directed mRNA cleavage by facilitating distinct steps in the assembly of the RNA-induced silencing complex (RISC). AGO2 is a RISC component that both carries out transcript cleavage and facilitates RISC maturation. Other factors appear to function as regulators of RISC assembly rather than as core factors for RNAi.
Kim
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Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Lee
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Harris
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Nakahara
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Carthew
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D000818:Animals; D060565:Argonaute Proteins; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D020365:RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C478068:R2D2 protein, Drosophila; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C478069:DCR-2 protein, Drosophila; C515033:Dcr-1 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases