Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Program in Molecular Medicine; Department of Cell Biology
Medical Subject Headings
Animals; Animals, Genetically Modified; Caenorhabditis elegans; DNA Primers; Drosophila; Embryo, Nonmammalian; Female; *Gene Expression Regulation, Developmental; Gene Silencing; Genes, Helminth; Genes, Reporter; Genomic Imprinting; Heterozygote; Larva; Luciferases; *Phylogeny; Polymerase Chain Reaction; RNA, Helminth
Life Sciences | Medicine and Health Sciences
RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of 22 nt that regulate stage-specific development. Here we show that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.
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Citation: Cell. 2001 Jul 13;106(1):23-34.