Molecular and cellular biology of the multifunctional protein P54NRB/NONO

在过去的十年里，基因组学的出现带来了两个重大的惊喜。首先，人类的蛋白质编码基因总数与果蝇或其他动物没有明显不同。其次，被认为在基因和蛋白质之间起中介作用的RNA分子，实际上比预期的要丰富得多。这些RNA物种中的许多并不像以前认为的那样是转录的“噪音”，而是发挥着多样化和重要的细胞功能，要么与细胞管家有关，要么与调节有关。人们对新的“RNA世界”知之甚少，但大多数时候，这些分子与我们细胞中的蛋白质结合在一起。我们有独特的机会深入分析P54NRB，这是一种参与RNA分子生产和加工的主要蛋白质。这种蛋白质在细胞核中起作用，也就是在RNA工厂的核心。我们自己和其他团队的结果表明，P54NRB与不同类型的RNA分子结合，这些相互作用在细胞周期中有所不同。我们希望了解是如何以及为什么这样做的。我们将继续对P54NRB进行分子解剖。换句话说，我们将分析这种蛋白质的每一段对各种RNA相互作用的贡献，并试图了解细胞是如何调节这个网络的。我们的工作将有助于更好地理解基本的细胞过程，如细胞分裂、基因表达和蛋白质-RNA相互作用。

In the last decade, two major surprises arose with the emergence of genomics. First, the overall number of protein-coding genes in humans is not markedly different from that of the fruit fly or other animals. Second, the RNA molecules, thought to play an intermediary role between the genes and the proteins, are in fact much more abundant than anticipated. Many of these RNA species are not transcriptional "noise", as previously thought, but play diversified and important cellular functions, either related to cell housekeeping or regulation. Little is known on the new "RNA world" but most of the time, these molecules are bound to proteins in our cells. We have the unique opportunity to analyze in depth P54NRB, a major protein involved in the production and processing of RNA molecules. This protein works in the cell nucleus, that is in the very heart of the RNA factory. Our own results and that of other groups showed that P54NRB binds to different types of RNA molecules and that these interactions vary during the cell cycle. We wish to understand how and why. We will proceed to the molecular dissection of P54NRB. In other words, we will analyze the contribution of every segment of this protein to the various RNA interactions and try to understand how the cell regulates this network. Our work will contribute to a better understanding of basic cellular processes such as cell division, gene expression and protein-RNA interactions.