MicroRNA regulation of biological mechanisms

我们最近已经了解了大量关于一类小的非编码的机制和生物学 RNA称为microRNA。这类引人注目的RNA构成了人类基因组中1%的基因， 它们抑制蛋白质编码基因的表达。这在动物物种中主要是通过 3'端含有互补序列的信使合成蛋白质的减弱 未翻译的区域虽然很难估计microRNA调控的程度，但从4 - 20%的 蛋白质编码基因可能直接由microRNA控制。模式生物的遗传学研究 支持microRNA在细胞和生物体生物学中发挥选择作用的观点。我们有兴趣 了解microRNA如何特异性抑制其靶基因及其生物学后果 调控为此，我们开发了一种方法来检测整个果蝇组织中的单个microRNA 和胚胎进行原位杂交。我们将评估78种已知果蝇的表达模式， 眼睛发育过程中的microRNA调控microRNA表达的上游调控途径 将评估这些通路在眼睛中的作用，并将其与这些通路的已知生物学功能相关联。我们将使用 microRNA基因突变以确定microRNA是否参与这些生物过程。一 将使用计算机模拟和分子遗传学方法的组合来鉴定和表征直接 microRNA抑制的靶点，并研究控制microRNA特异性的机制。 介导的翻译抑制。我们的目标是破译microRNA调控的规则， 以及身体不同组织的生物特异性。microRNA的联合作用可能会影响 许多人类基因的表达和microRNA的错误调节可能是复杂疾病的基础 如癌症易感性和进展的现象。

We have learned a great deal recently about the mechanism and biology of a class of small non-coding RNAs called microRNAs. This remarkable class of RNAs constitute 1 % of the genes in the human genome, and they repress the expression of protein-coding genes. This is achieved in animal specieis primarily by attenation of protein synthesis from messages which contain complementary sequence in their 3' untranslated regions. Although it is difficult to estimate the extent of microRNA regulation, from 4 - 20% of protein-coding genes might be directly controlled by microRNAs. Genetic studies in model organisms support the notion that microRNAs play select roles in cell and organismal biology. We are interested in understanding how microRNAs specifically inhibit their target genes and the biological consequences of this regulation. To this end, we developed a method to detect individual microRNAs in whole Drosophila tissues and embryos by in situ hybridization. We will evaluate the expression patterns of the 78 known Drosophila microRNAs during eye development. The upstream regulatory pathways that regulate microRNA expression in the eye will be evaluated, and correlated to known biological functions of these pathways. We will use microRNA gene mutagenesis to determine if microRNAs are involved in these biological processes. A combination of in silico and molecular genetic approaches will be used to identify and characterize direct targets of microRNA repression, and to investigate the mechanism(s) governing the specificity of microRNA- mediated translational repression. Our goal is to decipher the rules of microRNA regulation regarding target and biological specificity in diverse tissues of the body. The combined effects of microRNAs may affect the expression of many human genes, and misregulation of microRNAs may well underlie complex disease phenomena such as cancer susceptibility and progression.