Characterization of macromolecular complexes regulating let-7 microRNA biogenesis

基因表达是利用基因信息合成功能性基因产物（蛋白质或RNA）的过程。基因表达的调控是一种现象，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。最近的几项发现表明，RNA是基因表达的关键调节因子。特别是，最近发现的一种特殊类型的rna，称为microrna，现在被视为调节多细胞生物基因表达的最大分子群之一。在人类中，细胞中这些microrna的水平受到高度调节，以允许适当的发育，细胞中microrna水平的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microRNA生物发生过程中发生的这种调节的细节仍有待了解。我们研究计划的长期目标是对控制microrna生物发生的特定调控机制有一个基本的了解。我们目前的重点是let-7 microRNAs家族，这是第一批被鉴定的microRNAs。let-7 microrna在人类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的生物发生受特定蛋白的调控。在接下来的五年中，我们将进行科学研究，以更好地了解选择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生物发生的总体理解提供关键的见解，microRNA生物发生是自然科学中仍未完全理解的基本细胞过程。此外，我们的研究还可以帮助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.