Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Dev Cell. 2010 Jan 19;18(1):102-13. doi: 10.1016/j.devcel.2009.11.011.
RNaseIII ribonucleases act at the heart of RNA silencing pathways by processing precursor RNAs into mature microRNAs and siRNAs. In the fission yeast Schizosaccharomyces pombe, siRNAs are generated by the RNaseIII enzyme Dcr1 and are required for heterochromatin formation at centromeres. In this study, we have analyzed the subcellular localization of Dcr1 and found that it accumulates in the nucleus and is enriched at the nuclear periphery. Nuclear accumulation of Dcr1 depends on a short motif that impedes nuclear export promoted by the double-stranded RNA binding domain of Dcr1. Absence of this motif renders Dcr1 mainly cytoplasmic and is accompanied by remarkable changes in gene expression and failure to assemble heterochromatin. Our findings suggest that Dicer proteins are shuttling proteins and that the steady-state subcellular levels can be shifted toward either compartment.
RNaseIII 核糖核酸酶通过将前体 RNA 加工成成熟的 microRNA 和 siRNA，在 RNA 沉默途径中发挥核心作用。在裂殖酵母 Schizosaccharomyces pombe 中，siRNA 由 RNaseIII 酶 Dcr1 产生，并需要在着丝粒处形成异染色质。在这项研究中，我们分析了 Dcr1 的亚细胞定位，发现它在细胞核中积累，并在核周富集。Dcr1 的核积累依赖于一个短的基序，该基序阻止 Dcr1 的双链 RNA 结合域促进的核输出。这个基序的缺失使 Dcr1 主要位于细胞质中，并伴随着显著的基因表达变化和异染色质组装失败。我们的发现表明 Dicer 蛋白是穿梭蛋白，并且细胞内的稳定亚细胞水平可以向任一隔室转移。
