The Structure and Function of Perinucleolar Compartment

我们的长期目标是了解PNC的结构和功能及其在恶性肿瘤中的作用。的 核仁周室（PNC）是一种多组分的非膜结合核亚结构， 定位于核仁外围。我们已经发现它是恶性转化所独有的， 和体内。PNC富含由pol III新合成的RNA和RNA结合蛋白， 参与pol II RNA加工。我们的初步研究结果表明，PNC相关的RNA是在 与一些已知的pol II RNA结合蛋白形成相同的复合物。这些新的复合物不是 限制于PNC，因为PTB-MRP RNA相互作用也可以在没有PNC的正常细胞中检测到。 然而，这些复合物的水平或调节可能在恶性肿瘤期间发生变化，从而导致恶性肿瘤的发生。 这些复合物在PNC中的成核。这些发现导致我们的工作模式，其中PNC是 与新的分子复合物有关，并可能代表新的分子复合物的变化， 在恶性肿瘤期间新合成的pol III RNA的代谢。本提案的目标是开始测试 这一假设通过鉴定和初步表征这些新的RNP，使用RNase MRP RNA（ 第一个例子，并通过开始解决职能问题， 使用细胞生物学方法将这些RNP与PNC相关联。因为我们对 pol III小的非编码RNA的转录后加工和调节， 新的RNP不仅对理解PNC的结构和功能很重要，而且还应该揭示 一种新的机制参与这些功能RNA的转录后调控。

Our long-term goal is to understand the structure and function of the PNC and its roles in malignancy. The perinucleolar compartment (PNC) is a multicomponent non-membrane bound nuclear substructure that localizes to the nucleolar periphery. We have found it to be unique to malignant transformation both in vitro and in vivo. The PNC is enriched with RNA newly synthesized by pol III and RNA binding proteins primarily implicated in pol II RNA processing. Our preliminary findings show that the PNC-associated RNAs are in the same complexes with some of the known pol II RNA binding proteins. These novel complexes are not restricted to the PNC since PTB-MRP RNA interactions can also be detected in normal cells without PNCs. However, the levels or the regulations of these complexes may change during malignancy, leading to the nucleation of these complexes in the PNC. These findings lead to our working model in which the PNC is associated with and may represent changes in novel molecular complexes that are involved in the metabolism of newly synthesized pol III RNA during malignancy. The goal of this proposal is to begin test this hypothesis by identifying and initially characterizing these novel RNPs, using RNase MRP RNA (one of the bona fide components of the PNC) as the first example, and by beginning to address the functional association of these RNPs with the PNC using cell biological approaches. As little is understood regarding the post-transcriptional processing and regulation of the pol III small non-coding RNAs, the solution of the novel RNPs is not only important for the understanding of PNC structure and function, but should also reveal a novel mechanism involved in the post-transcriptional regulation of these functional RNAs.