a Martienssen Lab, Cold Spring Harbor Laboratory , Cold Spring Harbor , NY , USA.
b Genome Dynamics Unit, UMR 3525 CNRS, Institut Pasteur , Paris , France.
Cell Cycle. 2017 Sep 17;16(18):1643-1653. doi: 10.1080/15384101.2017.1361568. Epub 2017 Aug 28.
The nucleolus is a distinct compartment of the nucleus responsible for ribosome biogenesis. Mis-regulation of nucleolar functions and of the cellular translation machinery has been associated with disease, in particular with many types of cancer. Indeed, many tumor suppressors (p53, Rb, PTEN, PICT1, BRCA1) and proto-oncogenes (MYC, NPM) play a direct role in the nucleolus, and interact with the RNA polymerase I transcription machinery and the nucleolar stress response. We have identified Dicer and the RNA interference pathway as having an essential role in the nucleolus of quiescent Schizosaccharomyces pombe cells, distinct from pericentromeric silencing, by controlling RNA polymerase I release. We propose that this novel function is evolutionarily conserved and may contribute to the tumorigenic pre-disposition of DICER1 mutations in mammals.
核仁是细胞核中负责核糖体生物发生的一个独特隔室。核仁功能和细胞翻译机制的失调与疾病有关，特别是与许多类型的癌症有关。事实上，许多肿瘤抑制因子（p53、Rb、PTEN、PICT1、BRCA1）和原癌基因（MYC、NPM）直接在核仁中发挥作用，并与 RNA 聚合酶 I 转录机制和核仁应激反应相互作用。我们已经确定 Dicer 和 RNA 干扰途径在静息的酿酒酵母细胞的核仁中具有重要作用，这与着丝粒周围沉默不同，通过控制 RNA 聚合酶 I 的释放。我们提出，这种新功能在进化上是保守的，可能有助于哺乳动物中 DICER1 突变的致瘤倾向。
