Control of chromatin structure by long non-coding RNA

长链非编码RNA控制染色质结构

基本信息

批准号：
8757272
负责人：
Andrzej Tomasz Wierzbicki
金额：
$ 29.47万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8757272
关键词：
Affect Animal Model Animals Arabidopsis Binding Biology Cells Chromatin Chromatin Remodeling Factor Chromatin Structure Chromosome Structures Chromosomes Complex Congenital Disorders DNA DNA Methylation DNA Methyltransferase DNA Modification Methylases DNA Polymerase II DNA-Directed RNA Polymerase Defect Development Developmental Process Disease Environment Etiology Event Foundations Functional RNA Future Gene Expression Gene Expression Regulation Gene Silencing Genes Genetic Transcription Genome Genomic Imprinting Germ Lines Goals Higher Order Chromatin Structure Homeobox Genes Introns Knowledge Malignant Neoplasms Mammals Mediating Medical Modeling Molecular Mouse-ear Cress Mutate Nucleosomes Organism Pathway interactions Physiological Processes Plant Model Plants Polymerase Population Positioning Attribute Process Production Proteins RNA RNA-Binding Proteins Recruitment Activity Regulation Research Ribosomal RNA Small Interfering RNA Small Nuclear RNA System Testing Tissues Transcript Transfer RNA Untranslated Regions Vascular Plant Vertebrates Work X Inactivation base chromatin modification expectation histone modification human disease piRNA public health relevance response scaffold three dimensional structure tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY Non-coding RNAs are ribonucleic acids that do not encode proteins. Some non-coding RNAs are well understood (introns, UTRs, rRNA, tRNA etc.), others are much more mysterious. Recent work implicated non-coding RNAs in regulation of genes important for development and response to environment. The long term goal of this proposal is to better understand how long non-coding RNAs control genome activity by affecting chromatin structure. We will study the molecular mechanisms of RNA-mediated control of chromatin structure using a plant model organism, Arabidopsis thaliana. Plants are especially well suited for studying this conserved process because like metazoans they have complex development. They also contain specialized RNA Polymerases producing long non-coding RNAs necessary for transcriptional gene silencing. These polymerases can be mutated without affecting viability of the organism. We will use the unique opportunity to specifically manipulate production of long non-coding RNAs by mutating the polymerases to study the mechanisms of long non-coding RNA-mediated changes in chromatin structure. We will determine how long non-coding RNA controls gene activity by active nucleosome positioning. We will test if long non-coding RNA is involved in delimiting heterochromatic domains. We will also establish how long non-coding RNA affects three-dimensional structure of chromatin. Non-coding RNAs are involved in genomic imprinting, X-chromosome inactivation, regulation of homeotic genes and several other essential developmental and physiological processes. Defects in their functions are implicated in human disease. Precise control of chromatin structure is also required for proper development and has been implicated in cancer and several congenital disorders. Explaining the conserved molecular mechanisms of non-coding RNA- mediated control of chromatin structure will contribute to better understanding of disorders involving aberrant non-coding transcription and chromatin. We hope that it will contribute to the development of future treatments.

描述（由申请人提供）：项目摘要非编码 RNA 是不编码蛋白质的核糖核酸。一些非编码 RNA 已为人们所熟知（内含子、UTR、rRNA、tRNA 等），而另一些则更加神秘。最近的研究表明，非编码 RNA 参与了对发育和环境响应很重要的基因的调节。该提案的长期目标是更好地了解非编码 RNA 通过影响染色质结构来控制基因组活性多长时间。我们将使用植物模型生物拟南芥来研究 RNA 介导的染色质结构控制的分子机制。植物特别适合研究这种保守的过程，因为它们像后生动物一样具有复杂的发育。它们还含有专门的 RNA 聚合酶，可产生转录基因沉默所需的长非编码 RNA。这些聚合酶可以发生突变而不影响生物体的活力。我们将利用这个独特的机会，通过聚合酶突变来专门操纵长非编码 RNA 的产生，以研究长非编码 RNA 介导的染色质结构变化的机制。我们将通过主动核小体定位来确定非编码 RNA 控制基因活性的时间。我们将测试长非编码 RNA 是否参与界定异染色质结构域。我们还将确定非编码 RNA 影响染色质三维结构的时间长度。非编码 RNA 参与基因组印记、X 染色体失活、同源异型基因的调节以及其他一些重要的发育和生理过程。它们的功能缺陷与人类疾病有关。染色质结构的精确控制也是正常发育所必需的，并且与癌症和几种先天性疾病有关。解释非编码RNA介导的染色质结构控制的保守分子机制将有助于更好地理解涉及异常非编码转录和染色质的疾病。我们希望它将有助于未来治疗方法的发展。