Dual role for argonautes in MicroRNA processing and Posttranscriptional regulation of MicroRNA expression
Dual role for argonautes in MicroRNA processing and Posttranscriptional regulation of MicroRNA expression
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DOI：
10.1016/j.cell.2007.10.032
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发表时间：
2007-12-14
期刊：
影响因子：
64.5
通讯作者：
Haber, Daniel A.
中科院分区：
文献类型：
--
作者：
Diederichs, Sven;Haber, Daniel A.
microRNA是参与转录后基因调控的小的内源性非编码RNA。在microRNA生物发生过程中，Drosha和Dicer通过前体发夹（pre-miRNA）将初级转录物（pri-miRNA）加工成成熟的miRNA。miRNA与Argonaute蛋白（RNA干扰（RNAi）中的效应分子）结合到RNA诱导沉默复合物（RISC）中。在这里，我们表明，所有Argonautes提高成熟的miRNA表达转录后，独立的RNase活性。此外，我们还鉴定了RISC切割器Argonaute 2（Ago 2）在将pre-miRNA切割成额外的加工中间体（称为Ago 2切割的前体miRNA或ac-pre-miRNA）中的作用。这种内源性途径上的中间体是由前体miRNA发夹12个核苷酸从其3 '端切割而产生的。通过与siRNA加工类似，Ago 2切割可以促进在成熟后从RISC去除带切口的乘客链。Argonautes在RNAi效应阶段和miRNA生物发生和成熟中的多重作用表明microRNA表达和功能的协调调节。
MicroRNAs are small endogenous noncoding RNAs involved in posttranscriptional gene regulation. During microRNA biogenesis, Drosha and Dicer process the primary transcript (pri-miRNA) through a precursor hairpin (pre-miRNA) to the mature miRNA. The miRNA is incorporated into the RNA-Induced Silencing Complex (RISC) with Argonaute proteins, the effector molecules in RNA interference (RNAi). Here, we show that all Argonautes elevate mature miRNA expression posttranscriptionally, independent of RNase activity. Also, we identify a role for the RISC slicer Argonaute2 (Ago2) in cleaving the pre-miRNA to an additional processing intermediate, termed Ago2 cleaved precursor miRNA or ac-pre-miRNA. This endogenous, on-pathway intermediate results from cleavage of the pre-miRNA hairpin 12 nucleotides from its 3'-end. By analogy to siRNA processing, Ago2 cleavage may facilitate removal of the nicked passenger strand from RISC after maturation. The multiple roles of Argonautes in the RNAi effector phase and miRNA biogenesis and maturation suggest coordinate regulation of microRNA expression and function.