Encyclopedia of C elegans 3'UTRS and their regulatory elements

线虫百科全书 3UTRS 及其调控元件

基本信息

批准号：
7614463
负责人：
Fabio Piano
金额：
$ 38.07万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-04 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7614463
关键词：
3&apos Untranslated Regions Affect Alternative Splicing Amino Acid Motifs Animal Model Animals Area Binding Biological Caenorhabditis elegans Cataloging Catalogs Cells Cobalt Code Collection Complex Computer Analysis Computer Simulation Conserved Sequence Custom DNA DNA mapping Data Development Elements Employee Strikes Event Expressed Sequence Tags Functional RNA Gene Expression Gene Expression Regulation Genes Genome Genomics Goals Grant Hybrids In Vitro Indium Informatics Laboratories Lead Maps Medicine Messenger RNA MicroRNAs Microarray Analysis Modeling Open Reading Frames Post-Transcriptional Regulation Promoter Regions Protein Binding Protein Binding Domain Proteins RNA-Binding Proteins Race Regulation Regulatory Element Resolution Rest Role Site Staging System Technology Time Tissues Trans-Activators Transcript Transcriptional Regulation Untranslated Regions Variant Yeasts base comparative genome-wide in vivo

项目摘要

DESCRIPTION (provided by the applicant): We have organized a "3'UTRome Consortium" whose modENCODE goal is to map all 3' untranslated regions (3'UTRs) and their functional sequence elements in C. elegans. 3'UTRs are DNA encoded elements that are co-transcribed along with mRNAs and whose role is to regulate the activity of mRNA. We currently have only a partial and biased view of the global 3'UTRs sequences (3'UTRome) for any metazoan and have even less information on the motifs in the 3'UTRs that are used by trans-acting factors to drive gene regulation. Yet, what is known reveals a high level of complexity where 3'UTRs are often tissue-specific or are subject to alternative splicing events that lead to 3'UTR sequence diversity that parallels the diversity seen within the coding region of the transcript. Small non-coding RNAs (eg. microRNAs) are a class of posttranscriptional regulators that function through motifs found in the 3'UTRs; however only a subset of 3'UTR::microRNA motifs are though to be known. MicroRNAs add to the previously established fundamental role of RNA-binding proteins known to regulate expression; however, even less is known about these protein-binding motifs. C. elegans provides an excellent model to reveal the DNA-encoded functional elements that drive these complex events in a system where the genome is completely mapped and where 3'UTRs are comparatively compact. We propose to build on our preliminary studies and use a combination of in vitro, in vivo and in silico approaches to identify most or all 3'UTRs and functional sequence elements within them. Specifically, we propose to use genome-wide RT-PCR-based strategies to identify all 3'UTRs in C. elegans; to use computational approaches, microarray analysis and deep sequencing to reveal the vast majority of 3'UTR::microRNA binding motifs and use RIP-CHIP, Yeast-3-Hybrid and computational analysis to map the 3'UTR::RNA-binding-Protein motifs. To use genome data in medicine we need to build a map of the DNA elements that could affect every gene's activity. We are proposing to build a critical part of such a map using the model animal C. elegans by identifying all the 3'UTRs (sequence elements that regulate gene expression) as well as dissect the 3'UTRs and identify sub-elements that are responsible for the 3'UTR's functions.

描述（由申请人提供）：我们组织了一个“ 3'Utrome Consortium”，其调节码的目标是在秀丽隐杆线虫中绘制所有3'未翻译区域（3'UTR）及其功能序列元素。 3'Utrs是与mRNA共转录的DNA编码元素，其作用是调节mRNA的活性。目前，对于任何后生动物，我们对全局3'UTRS序列（3'Utrome）的偏见和有偏见的看法甚至更少，并且对3'UTR中的基序的信息较少，而反式作用因子使用的3'UTRS来驱动基因调节。然而，众所周知的揭示了3'UTR通常是组织特异性或受到导致3'UTR序列多样性的替代剪接事件的高度复杂性，这些剪接事件与转录本中编码区域内看到的多样性相同。小型非编码RNA（例如microRNA）是一类通过3'UTR中发现的基序的转录后调节剂；但是，只有3'UTR :: microRNA图案的子集是已知的。 MicroRNA增加了已知可以调节表达的RNA结合蛋白的先前确定的基本作用；然而，对于这些蛋白质结合基序甚至知之甚少。秀丽隐杆线虫提供了一个出色的模型，以揭示DNA编码的功能元素，这些功能元件在完全映射基因组并相对紧凑的系统中驱动这些复杂事件。我们建议以初步研究为基础，并结合体外，体内和计算机方法，以识别其中的大多数或所有3'UTRS和所有功能序列元素。具体而言，我们建议使用基于全基因组的RT-PCR策略来识别秀丽隐杆线虫中的所有3'UTR。要使用计算方法，微阵列分析和深度测序揭示了3'UTR :: microRNA结合基序的绝大多数，并使用RIP-CHIP，YEAST-3-HYBRID和计算分析来映射3'UTR :: RNA结合蛋白基序。要在医学中使用基因组数据，我们需要建立可能影响每个基因活性的DNA元素的图。我们建议使用模型动物秀丽隐杆线虫来构建此类地图的关键部分，通过识别所有3'UTR（调节基因表达的序列元素），并解剖3'UTRS并识别负责3'UTR功能的子元素。