Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C-elegans developmental timing

被引:1465
作者
Grishok, A
Pasquinelli, AE
Conte, D
Li, N
Parrish, S
Ha, I
Baillie, DL
Fire, A
Ruvkun, G
Mello, CC [1 ]
机构
[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
[2] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA
[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
[5] Johns Hopkins Univ, Biol Grad Program, Baltimore, MD 21218 USA
[6] Simon Fraser Univ, Inst Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada
[7] Carnegie Inst Sci, Baltimore, MD 21210 USA
[8] Hanwha Chem R&D Inst, Daejun 305345, South Korea
关键词
D O I
10.1016/S0092-8674(01)00431-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:23 / 34
页数:12
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