Department of Cell Biology, Duke University Medical Center, Durham, NC 27708, USA.
Mol Cell. 2010 Apr 9;38(1):67-77. doi: 10.1016/j.molcel.2010.02.021.
Both splicing factors and microRNAs are important regulatory molecules that play key roles in posttranscriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of the splicing factor SF2/ASF. Here we show that SF2/ASF and one of its upregulated microRNAs (miR-7) can form a negative feedback loop: SF2/ASF promotes miR-7 maturation, and mature miR-7 in turn targets the 3'UTR of SF2/ASF to repress its translation. Enhanced microRNA expression is mediated by direct interaction between SF2/ASF and the primary miR-7 transcript to facilitate Drosha cleavage and is independent of SF2/ASF's function in splicing. Other miRNAs, including miR-221 and miR-222, may also be regulated by SF2/ASF through a similar mechanism. These results underscore a function of SF2/ASF in pri-miRNA processing and highlight the potential coordination between splicing control and miRNA-mediated gene repression in gene regulatory networks.
剪接因子和 microRNAs 都是重要的调控分子,它们在后转录基因调控中发挥着关键作用。通过 microRNA 深度测序,我们发现 40 个 microRNAs 在剪接因子 SF2/ASF 的异位过表达时表现出差异表达。在这里,我们表明 SF2/ASF 和其上调的 microRNA 之一(miR-7)可以形成负反馈回路:SF2/ASF 促进 miR-7 的成熟,而成熟的 miR-7 反过来靶向 SF2/ASF 的 3'UTR 以抑制其翻译。增强的 microRNA 表达是通过 SF2/ASF 与初级 miR-7 转录本之间的直接相互作用介导的,从而促进 Drosha 切割,并且不依赖于 SF2/ASF 在剪接中的功能。其他 microRNAs,包括 miR-221 和 miR-222,也可能通过类似的机制受到 SF2/ASF 的调节。这些结果强调了 SF2/ASF 在 pri-miRNA 加工中的功能,并突出了剪接控制和 miRNA 介导的基因抑制在基因调控网络中的潜在协调作用。