在發(fā)育過(guò)程中,一類被稱為“微RNA”的小型RNA在決定基因表達(dá)譜中扮演重要角色,,它們是通過(guò)與某些信使RNA結(jié)合、抑制這些信使RNA的翻譯或使其沉默的方式發(fā)揮作用的,。人們認(rèn)為,,微RNA是造成單細(xì)胞生物演化成多細(xì)胞生物的一個(gè)因素。
Saibal Chatterjee 和 Helge Großhans報(bào)告說(shuō),,在微RNA作用于一個(gè)目標(biāo)信使RNA之上,、并從沉默復(fù)合物中釋放出來(lái)之后,核糖核酸酶XRN-2促進(jìn)它們的降解,。XRN-2以這種方式來(lái)起微RNA含量的一種體內(nèi)平衡調(diào)控因子的作用,,這個(gè)作用在對(duì)新的發(fā)育提示信號(hào)做出反應(yīng)當(dāng)中可能具有重要性,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 461, 546-549 (24 September 2009) | doi:10.1038/nature08349
Active turnover modulates mature microRNA activity in Caenorhabditis elegans
Saibal Chatterjee1 & Helge Großhans1
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.