2009年10月21日 23:16  点击:[]


Saibal Chatterjee 和 Helge Gro ß hans报告说,在微RNA作用于一个目标信使RNA之上、并从沉默复合物中释放出来之后,核糖核酸酶XRN-2促进它们的降解。XRN-2以这种方式来起微RNA含量的一种体内平衡调控因子的作用,这个作用在对新的发育提示信号做出反应当中可能具有重要性。(生物谷


Nature461, 546-549 (24 September 2009) | doi:10.1038/nature08349

Active turnover modulates mature microRNA activity in Caenorhabditis elegans

Saibal Chatterjee1 & Helge Gro ß hans1

1 Friedrich Miescher Institute for Biomedical Research, PO Box 2543, CH-4002 Basel, Switzerland

Correspondence to: Helge Grohans1 Correspondence and requests for materials should be addressed to H.G.

MicroRNAs (miRNAs) constitute a large class of regulatory RNAs that repress target messenger RNAs to control various biological processes1. Accordingly, miRNA biogenesis is highly regulated, controlled at both transcriptional and post-transcriptional levels2, and overexpression and underexpression of miRNAs are linked to various human diseases, particularly cancers1, 3. As RNA concentrations are generally a function of biogenesis and turnover, active miRNA degradation might also modulate miRNA accumulation, and the plant 3'5' exonuclease SDN1 has been implicated in miRNA turnover4. Here we report that degradation of mature miRNAs in the nematode Caenorhabditis elegans, mediated by the 5'3' exoribonuclease XRN-2, affects functional miRNA homeostasis in vivo. We recapitulate XRN-2-dependent miRNA turnover in larval lysates, where processing of precursor-miRNA (pre-miRNA) by Dicer, unannealing of the miRNA duplex and loading of the mature miRNA into the Argonaute protein of the miRNA-induced silencing complex (miRISC) are coupled processes that precede degradation of the mature miRNA. Although Argonaute:miRNA complexes are highly resistant to salt, larval lysate promotes efficient release of the miRNA, exposing it to degradation by XRN-2. Release and degradation can both be blocked by the addition of miRNA target RNA. Our results therefore suggest the presence of an additional layer of regulation of animal miRNA activity that might be important for rapid changes of miRNA expression profiles during developmental transitions and for the maintenance of steady-state concentrations of miRNAs. This pathway might represent a potential target for therapeutic intervention on miRNA expression.

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