Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C-elegans developmental timing
Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C-elegans developmental timing
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DOI：
10.1016/s0092-8674(01)00431-7
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发表时间：
2001-07-13
期刊：
影响因子：
64.5
通讯作者：
Mello, CC
中科院分区：
文献类型：
--
作者：
Grishok, A;Pasquinelli, AE;Mello, CC
RNAi是由双链（ds）RNA触发的基因沉默现象，并且涉及引导mRNA破坏的21至26 nt RNA片段的产生。在秀丽隐杆线虫中，lin-4和let-7编码调节阶段特异性发育的22 nt的小时间RNA（stRNA）。在这里，我们表明，失活的基因相关的RNAi途径基因，果蝇Dicer（dcr-1）的同源物，和两个同源的rde-1（alg-1和alg-2），导致异时表型相似的lin-4和let-7突变。此外，我们表明dcr-1，alg-1和alg-2是lin-4和let-7 stRNA成熟和活性所必需的。我们的研究结果表明，一个共同的加工机制产生指导RNA介导RNAi和内源性基因调控。
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.