POST TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION IN THE LENS (LENS GENE EXPRESSION

晶状体基因表达的转录后控制（晶状体基因表达

基本信息

批准号：
8241900
负责人：
DAVID CY BEEBE
金额：
$ 47.8万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8241900
关键词：
3&apos Untranslated Regions Adult Alternative Splicing Bioinformatics Blindness Cataract Cell Differentiation process Cell Line Cells Code Complex Crystallins Cytoplasmic Granules Data Density Gradient Centrifugation Development Embryo Embryonic Development Epithelial Cells Epithelium Eye Fertilization Fiber Future Gametogenesis Gene Expression Genes Genetic Transcription Genetic Translation Health Human Immunoprecipitation In Vitro Individual Inherited Intermediate Filaments Lead Lens Fiber Lens Placodes Life Luciferases Mediating Membrane Proteins Messenger RNA Methods MicroRNAs Modeling Mus Mutation Neonatal Polyribosomes Post-Transcriptional Regulation Process Property Protein Binding Proteins Proteomics Public Health Publishing RNA RNA Sequences RNA chemical synthesis RNA, Messenger, Stored Refractive Indices Research Ribonucleoproteins Role Site Staging Stem cells Sucrose System Testing Tissue-Specific Gene Expression Tissues Transcript Transgenic Organisms Translating Translational Repression Translations Untranslated Regions Vesicle base cell type fiber cell gene discovery lens lens transparency novel postnatal selective expression tool transcription factor transcription termination

项目摘要

DESCRIPTION (provided by applicant): The lens depends for its function on the accumulation of large amounts of a modest number of proteins. These include cytoplasmic crystallins, specialized membrane proteins and intermediate filaments. For more than thirty years it has been assumed that the genes encoding these proteins are "turned on" during the formation of lens fiber cells, the cells that make up the bulk of the lens. However, the data presented in this proposal show that the RNAs encoding these "fiber-specific" proteins are synthesized early in lens formation and are present in the progenitor cells of the lens, the lens epithelial cells, throughout life. Since these mRNAs are present, but the proteins that they encode are not, there must be mechanisms that determine when and in what cells these mRNAs are translated into protein. Our data suggest that selective translation of these mRNAs is governed by protein-RNA complexes called RNA granules (RGs). We propose to identify the major genes that are regulated in the lens by post-transcriptional mechanisms, determine the RG components and RNA sequences required to regulate the expression of an abundant lens membrane protein, MIP, and to identify the lens-specific RG components that are responsible for the selective translation of the "fiber cell-specific" mRNAs throughout lens development and in postnatal life. We expect that these studies will define a new paradigm for lens gene expression and will serve as a model for post-transcriptional regulation of gene expression in other tissues. Since mutation of one lens-specific RG component, TDRD7, causes human cataracts, these studies will also provide fundamental information about cataract formation.

描述（由申请人提供）：镜头的功能取决于大量适度蛋白质的积累。这些包括细胞质晶体，专门的膜蛋白和中间丝。在三十多年来，人们一直认为编码这些蛋白质的基因在形成晶状体纤维细胞（构成大部分晶状体的细胞）过程中被“打开”。但是，本提案中提供的数据表明，编码这些“纤维特异性”蛋白的RNA在晶状体形成早期合成，并且存在于透镜的祖细胞中，透镜上皮细胞在整个生命中。由于存在这些mRNA，但是它们编码的蛋白质不是，因此必须有一些机制来确定这些mRNA被转化为蛋白质的细胞何时何地。我们的数据表明，这些mRNA的选择性翻译受称为RNA颗粒（RGS）的蛋白-RNA复合物的控制。我们建议通过转录后机制确定在镜头中调节的主要基因，确定调节丰富的透镜膜蛋白，MIP的表达所需的RG成分和RNA序列，以确定透镜特异性RG成分，这些RG成分负责“ Fiber Cell-cells-cell-spectific” MRNS的范围均遍布整体上的“ Fiber Cell-Spection”。我们预计这些研究将定义用于晶状体基因表达的新范式，并将作为其他组织中基因表达后转录后调节的模型。由于一种透镜特异性RG成分TDRD7的突变会导致人白内障，因此这些研究还将提供有关白内障形成的基本信息。