Encyclopedia of C elegans 3'UTRS and their regulatory elements

描述（由申请人提供）：我们已经组织了一个“3 'UTRome Consortium”，其modENCODE目标是在C.优雅3 'UTR是与mRNA一起沿着转录的DNA编码元件，其作用是调节mRNA的活性。我们目前对任何后生动物的全局3 'UTR序列（3' UTRome）只有部分和偏见的看法，并且对反式作用因子用于驱动基因调控的3 'UTR中的基序的信息更少。然而，已知的揭示了高水平的复杂性，其中3 'UTR通常是组织特异性的或经历导致3' UTR序列多样性的选择性剪接事件，所述多样性与转录物的编码区内所见的多样性平行。小的非编码RNA（例如，microRNA）是一类转录后调节因子，其通过在3 'UTR中发现的基序起作用;然而，仅知道3' UTR：：microRNA基序的子集。microRNA增加了先前建立的已知调节表达的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甚至更少。C.线虫提供了一个极好的模型来揭示DNA编码的功能元件，这些功能元件在基因组被完全定位并且3 'UTR相对紧凑的系统中驱动这些复杂事件。我们建议建立在我们的初步研究，并使用在体外，在体内和在硅片方法的组合，以确定大多数或所有的3 'UTR和功能序列元件内。具体而言，我们建议使用全基因组RT-PCR为基础的策略，以确定所有的3 'UTR在C。优雅的;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-CHIP、酵母-3-杂交和计算分析来绘制3' UTR：：RNA结合蛋白基序。 为了在医学中使用基因组数据，我们需要构建一个可能影响每个基因活性的DNA元件的图谱。我们建议使用模型动物C来构建这样一个地图的关键部分。通过鉴定所有的3 'UTR（调节基因表达的序列元件）以及解剖3' UTR并鉴定负责3 'UTR功能的子元件来鉴定线虫。

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.