Temporal Regulation of miR156

描述（由申请人提供）：微小RNA（miRNA）是短的非蛋白质编码RNA，其与近互补RNA序列结合以抑制基因表达。通过miRNA控制基因表达已经成为广泛生物体（蝇、蠕虫、植物和哺乳动物）中基因调控的重要机制以及治疗疾病的潜在工具。最近已经证明，miRNA在与细胞死亡、病毒感染、胰岛素分泌和癌症相关的人类病理状况的调节中发挥重要作用。此外，据估计，超过30%的人类基因由miRNA调控。miRNAs调控植物发育的许多方面。其中之一是发展阶段的变化过程。在它们发育的早期，拟南芥植物产生形态简单的幼叶。之后，它们经历一个被称为营养阶段的转变，开始产生更复杂的成年叶片。最后，植物开花，标志着植物发育的最后阶段。miR156是这一过程的主要调节因子。使用本提案中描述的实验，我将定义有助于miR156时间表达的因素。具体而言，我将： 目的1：利用miR156及其靶基因的突变等位基因确定miR156 a是否在时间上调节SPL表达。 目标2：开发用于启动子缺失研究和突变体筛选的报告基因，以鉴定参与miR156a时间调控的顺式和反式因子。 目的：通过筛选sqn的抑制子和增强子来鉴定调控miR156表达的基因。 这些研究的结果不仅有助于了解叶的发育，而且还将增加我们对时间调节机制的理解，这是所有生物体发育生物学中的一个关键过程。

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) are short, non-protein coding RNAs that bind to near complementary RNA sequences to inhibit gene expression. The control of gene expression by miRNAs has emerged as an important mechanism for gene regulation in a wide range of organisms (flies, worms, plants, and mammals) as well as a potential tool for treating disease. MiRNAs have recently been demonstrated to play an important role in the regulation of pathological conditions in humans related to cell death, viral infection, insulin secretion and cancer. Furthermore, it is estimated that over 30% of all human genes are regulated by miRNAs. MiRNAs regulate many aspects of plant development. Among these is the process of developmental phase change. Early in their development, Arabidopsis plants produce morphologically simple juvenile leaves. Later, they undergo a transition known as vegetative phase change and begin to produce more complex adult leaves. Finally, the plants produce flowers, marking the final stage of plant development. The miRNA, miR156, is a major regulator of this process. Using the experiments described in this proposal, I will define the factors that contribute to the temporal expression of miR156. Specifically, I will: AIM 1: Determine if miR156a temporally regulates SPL expression using mutant alleles of the miR156 and its targets. AIM 2: Develop reporters for use in promoter-deletion studies and mutant screens to identify cis- and transfactors involved in the temporal regulation of miR156a. AIMS: Identify genes that regulate miR156 expression by screening for suppressors and enhancers of sqn. The results of these studies will not only contribute to the understanding of leaf development, but will also increase our understanding of the mechanism of temporal regulation, a key process in developmental biology of all organisms.