Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.
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.
Grishok
A
A
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pasquinelli
A E
AE
Conte
D
D
Li
N
N
Parrish
S
S
Ha
I
I
Baillie
D L
DL
Fire
A
A
Ruvkun
G
G
Mello
C C
CC
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D017931:DNA Primers; D004330:Drosophila / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D017238:Genes, Helminth; D017930:Genes, Reporter; D018392:Genomic Imprinting; D006579:Heterozygote; D007814:Larva; D008156:Luciferases / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D018510:RNA, Helminth / Q000235:genetics*
D017931:DNA Primers; D018510:RNA, Helminth; D008156:Luciferases