Nuclear Retention of Fission Yeast Dicer Is a Prerequisite for RNAi-Mediated Heterochromatin Assembly

Nuclear Retention of Fission Yeast Dicer Is a Prerequisite for RNAi-Mediated Heterochromatin Assembly
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DOI:
10.1016/j.devcel.2009.11.011
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发表时间:
2010-01-19
期刊:
影响因子:
11.8
通讯作者:
Buehler, Marc
Buehler, Marc
中科院分区:
生物学1区
文献类型:
--
作者:
Emmerth, Stephan;Schober, Heiko;Buehler, Marc

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RNAselll核糖核酸酶通过将前体RNA加工成成熟的microRNA和siRNA,在RNA沉默途径的核心发挥作用。在裂殖酵母粟酒裂殖酵母中,siRNA 由 RNasell 酶 Dcr1 产生,并且是着丝粒异染色质形成所必需的。在本研究中,我们分析了Dcr1的亚细胞定位,发现它在细胞核中积累,并在核外围富集。 Dcr1 的核积累取决于一个短基序,该基序阻碍由 Dcr1 的双链 RNA 结合域促进的核输出。缺乏该基序使得 DCr1 主要存在于细胞质中,并伴有基因表达的显着变化和无法组装异染色质。我们的研究结果表明,Dicer 蛋白是穿梭蛋白,稳态亚细胞水平可以向任一区室转移。
RNaselll 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 RNaselll 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.