Characterization of macromolecular complexes regulating let-7 microRNA biogenesis

基因表达是基因信息被用于合成功能性基因产物（蛋白质或RNA）的过程。基因表达调控是一种现象，通过这种现象，遗传密码被解释为产生细胞、器官和生物体的特性。最近的几项发现使人们认为RNA是基因表达的关键调节因子。 特别是，最近发现的一种特定类型的RNA，称为microRNA，现在被视为调节多细胞生物体中基因表达的最大分子组之一。在人类中，这些microRNA在细胞中的水平受到高度调节，以允许适当的发育，而microRNA的细胞水平失调与几种疾病有关，包括癌症和神经系统疾病。现在很清楚，几种microRNA的水平在它们的形成过程中受到调节，这通常被称为它们的生物发生。然而，关于在microRNA生物合成过程中发生的这种调节的细节仍有很多未知之处。我们研究计划的长期目标是从根本上了解控制microRNA生物发生的特定调控机制。我们目前的重点是let-7家族的microRNA，这是第一个被确定的microRNA。let-7 microRNA在人类的正常生长中起着核心作用，可以阻止癌症的发展。众所周知，let-7家族的microRNA的生物合成受特定蛋白质的调控。在接下来的五年里，我们将进行科学研究，以更好地了解选择的蛋白质如何特异性调节let-7 microRNA家族的生物发生。我们的研究将为我们对microRNA生物发生的一般理解提供重要的见解，这是自然科学中的一个基本细胞过程，目前还没有完全理解。此外，我们的研究还有助于开发新的癌症治疗方法。

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product, either a protein or an RNA. The regulation of gene expression is a phenomenon by which the genetic code is interpreted to give rise to the properties of cells, organs and organisms. Several recent discoveries have led to the idea that RNA is a key regulator of gene expression. In particular, a specific type of recently discovered RNAs, termed microRNAs, are now viewed as one of the largest groups of molecules that regulate gene expression in multi-cellular organisms. In humans, the levels of these microRNAs in cells are highly regulated to allow for proper development, and dysregulation of cellular levels of microRNAs is linked to several diseases, including cancer and neurological diseases. It is now clear that the levels of several microRNAs are regulated during their formation, which is usually referred to as their biogenesis. However, much remains to be known about the details of this regulation that occur during microRNA biogenesis. The long-term objective of our research program is to gain a fundamental understanding of specific regulatory mechanism that control the biogenesis of microRNAs. Our current focus is on the let-7 family of microRNAs, which were among the first microRNAs to be identified. The let-7 microRNAs play a central role in normal growth in humans and can block the development of cancer. It is well known that the biogenesis of microRNAs from the let-7 family is regulated by specific proteins. In the next five years, we will perform scientific studies to better understand how select proteins specifically regulate the biogenesis of the let-7 family of microRNAs. Our studies will provide critical insights into our general understanding of microRNA biogenesis, a fundamental cellular process in the natural sciences that is still not completely understood. In addition, our studies could also help in the development of novel cancer therapeutics.