最新《Nature》microRNA新发现

　　

生物通报道，瑞士Friedrich Miescher研究所生物医学研究中心的科学家Saibal Chatterjee和Helge Grohans在最新一期的Nature杂志上发表microRNA的研究进展，Active turnover modulates mature microRNA activity in Caenorhabditis elegans。

 

研究发现miRNA的主要功能是调节生物体内在的与机体生长、发育、疾病发生过程有关的基因的表达，而且研究人员推测这种小分子调节着人类三分之一的基因！ miRNA还与艾滋病、白血病、糖尿病、畸形等病变有关。

 

Saibal Chatterjee 和 Helge Großhans报告说，在microRNA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microRNA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。

 

生物通推荐原文摘要

Nature 461, 546-549 (24 September 2009) | doi:10.1038/nature08349; Received 2 April 2009; Accepted 27 July 2009; Published online 6 September 2009

 

Active turnover modulates mature microRNA activity in Caenorhabditis elegans

Saibal Chatterjee1 & Helge Grohans1

 

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. (Email: [e-mail]).

 

 

【Abstract】

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.