Structure and function of the perinucleolar compartment in cancer cells.

Structure and function of the perinucleolar compartment in cancer cells.
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DOI:
10.1101/sqb.2010.75.026
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发表时间:
2010
期刊:
Cold Spring Harbor symposia on quantitative biology
影响因子:
--
通讯作者:
Huang S
Huang S
中科院分区:
其他
文献类型:
--
作者:
Slusarczyk A;Kamath R;Wang C;Anchel D;Pollock C;Lewandowska MA;Fitzpatrick T;Bazett-Jones DP;Huang S

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核周间隔(PNC)是一种在癌细胞中形成的亚核小体。使用人体肿瘤组织进行的活体分析表明,结直肠癌的PNC患病率与疾病进展密切相关,而PNC患病率高与患者预后不良相关。这些发现与之前在乳腺癌和体外癌细胞系中观察到的结果一致。PNC由粗股组成,形成一个丝状网络,通常延伸到核仁中。虽然透射电子显微镜(TEM)观察到它似乎是电子致密的,但电子能谱所成像的结构的实际密度要低得多,类似于染色质间的空间,并且排列着核糖核蛋白(RNPs)。原位检测表明,PNC高度富含一组源于聚合酶III(Pol III)的小RNA和主要参与前mRNA加工的RNA结合蛋白。一种新的凝胶移动方法表明,在HeLa细胞裂解产物中加入PNC相关的RNA增加了天然凝胶电泳中多嘧啶结合(PTB)蛋白的迁移率,表明这些RNAs与PTB蛋白之间存在相互作用。在这些和其他发现的基础上,我们提出了一个工作模型,在该模型中,新的RNP在调节癌细胞中PNC的基因表达方面具有关键作用。
The perinucleolar compartment (PNC) is a subnuclear body that forms in cancer cells. In vivo analyses using human tumor tissues demonstrate a close correlation between PNC prevalence and disease progress in colorectal carcinoma, and a high PNC prevalence is associated with poor patient outcome. These findings are consistent with previous observations in breast cancer and cancer cell lines in vitro. The PNC is composed of thick strands that form a filamental meshwork often extending into the nucleolus. Although it appears to be electron dense as observed by transmission electron microscopy (TEM), the actual density of the structure imaged by electron spectroscopy is much lower, similar to that of the interchromatin space, and is lined with ribonucleoproteins (RNPs). In situ detections show that the PNC is highly enriched with a subset of small RNAs of polymerase III (Pol III) origins and RNA-binding proteins primarily implicated in pre-mRNA processing. A novel gel-shifting approach demonstrates that the addition of PNC-associated RNAs into HeLa cell lysates increases the mobility of polypyrimidine tract-binding (PTB) protein in a native gel electrophoresis, suggesting an interaction between these RNAs and PTB proteins. On the basis of these and other findings, we propose a working model in which novel RNPs have a key role in regulating gene expression at the PNC in cancer cells.
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