生物谷報道：Dicer蛋白是SiRNA發(fā)揮作用中的至關(guān)重要蛋白,。同樣SiRNA機制在生物體的發(fā)育中同樣起著重要作用,，那么,，如果將Dicer敲除了呢？這種奇思妙想,，促進了本周剛剛出版的PNAS上一篇文章,。同時，Dicer缺乏可以直接了解RNAi在發(fā)育過程中可能扮演著何種重要角色,，為這一關(guān)鍵問題提供了良好的線索,。
Dicer is an RNase III-family nuclease that initiates RNA interference (RNAi) and related phenomena by generation of the small RNAs that determine the specificity of these gene silencing pathways. We have previously shown that Dicer is essential for mammalian development, with Dicer-deficient mice dying at embryonic day 7.5 with a lack of detectable multipotent stem cells. To permit a more detailed investigation of the biological roles of Dicer, we have generated embryonic stem cell lines in which their single Dicer gene can be conditionally inactivated. As expected, Dicer loss compromises maturation of microRNAs and leads to a defect in gene silencing triggered by long dsRNAs. However, the absence of Dicer does not affect the ability of small interfering RNAs to repress gene expression. Of interest, Dicer loss does compromise the proliferation of ES cells, possibly rationalizing the phenotype previously observed in Dicer-null animals. Dicer loss also affects the abundance of transcripts from mammalian centromeres but does so without a pronounced affect on histone modification status at pericentric repeats or methylation of centromeric DNA. These studies provide a conditional model of RNAi deficiency in mammals that will permit the dissection of the biological roles of the RNAi machinery in cultured mammalian cells.
Characterization of Dicer-deficient murine embryonic stem cells
Elizabeth P. Murchison *, Janet F. Partridge , Oliver H. Tam *, Sihem Cheloufi * and Gregory J. Hannon *,
