Encyclopedia of C elegans 3'UTRS and their regulatory elements

描述(由申请人提供)：我们组织了一个“3‘UT罗马联盟”，其modENCODE目标是定位线虫中所有3’非翻译区(3‘UTRs)及其功能序列元件。3‘UTRs是与mRNAs共转录的DNA编码元件，其作用是调节mRNAs的活性。我们目前对任何后生动物的全球3‘UTRS序列(3’UT罗马)只有部分和偏见的看法，而关于反式作用因子用来驱动基因调控的3‘UTRs中的基序的信息更少。然而，已知的情况揭示了高度的复杂性，其中3‘UTRs通常是组织特异性的，或者受到替代剪接事件的影响，这些剪接事件导致3’UtR序列多样性，这与转录本编码区内的多样性平行。小的非编码RNA(如MicroRNAs)是一类转录后调控因子，通过3‘UTRs中的基序发挥作用；然而，目前只有3’UTR：：microRNA基序的子集已知。MicroRNAs增加了已知的调节表达的RNA结合蛋白的基本作用；然而，对这些蛋白质结合基序的了解更少。线虫提供了一个很好的模型来揭示DNA编码的功能元件，这些功能元件在一个基因组完全被绘制并且3‘UTRs相对紧凑的系统中驱动这些复杂的事件。我们建议在我们的初步研究的基础上，使用体外、体内和电子计算机相结合的方法来鉴定它们中的大多数或所有3‘UTRs和功能序列元件。具体地说，我们建议使用基于全基因组RT-PCR的策略来识别线虫中的所有3‘UTRs；使用计算方法、微阵列分析和深度测序来揭示绝大多数3’UTR：：microRNA结合基序，并使用RIP芯片、酵母3-杂交和计算分析来定位3‘UTR：RNA结合蛋白基序。 为了在医学上使用基因组数据，我们需要建立一张可能影响每个基因活动的DNA元素的图谱。我们建议使用模式动物线虫来构建这种图谱的关键部分，方法是识别所有3‘UTRs(调控基因表达的序列元件)，并剖析3’UTRs并识别负责3‘UTRs功能的亚元件。

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.