Zhang Xiaoxiao, Graves Paul R, Zeng Yan
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Biochim Biophys Acta. 2009 Feb;1789(2):153-9. doi: 10.1016/j.bbagrm.2008.11.004. Epub 2008 Nov 21.
microRNAs are a class of small RNA molecules that associate with Argonaute proteins to regulate gene expression. Argonaute proteins not only mediate the functions of microRNAs, but also play an essential role in the biogenesis of microRNAs. Here, we report that stable, long-term overexpression of Argonaute2, an Argonaute isoform, induces the production of a number of microRNAs, such as the let-7 family of microRNAs, in 293T cells. On the other hand, the expression of many microRNAs is insensitive to elevated Argonaute levels, and microRNAs in the miR-17-92 and homologous clusters are even down-regulated. The down-regulation may result from the let-7-mediated inhibition of the expression of Myc, which positively controls the transcription of the microRNAs clusters. Our data suggest that human cells have a mechanism for microRNA homeostasis, and that overexpression of a general microRNA processing factor can differentially regulate the expression of specific microRNAs.
微小RNA是一类与AGO蛋白结合以调控基因表达的小RNA分子。AGO蛋白不仅介导微小RNA的功能，还在微小RNA的生物合成中起关键作用。在此，我们报道AGO亚型AGO2在293T细胞中的稳定、长期过表达可诱导多种微小RNA的产生，如微小RNA的let-7家族。另一方面，许多微小RNA的表达对AGO水平升高不敏感，miR-17-92及其同源簇中的微小RNA甚至下调。这种下调可能是由于let-7介导的Myc表达抑制所致，Myc可正向调控微小RNA簇的转录。我们的数据表明，人类细胞具有微小RNA稳态机制，并且一般微小RNA加工因子的过表达可差异调节特定微小RNA的表达。
