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'UTRome 联盟”，其 modENCODE 目标是绘制线虫中所有 3' 非翻译区 (3'UTR) 及其功能序列元件的图谱。 3'UTR 是与 mRNA 共同转录的 DNA 编码元件，其作用是调节 mRNA 的活性。目前，我们对任何后生动物的全局 3'UTR 序列 (3'UTRome) 仅有部分和有偏见的看法，并且对反式作用因子用于驱动基因调控的 3'UTR 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'UTR 通常是组织特异性的，或者受到选择性剪接事件的影响，从而导致 3'UTR 序列多样性，与转录本编码区域内看到的多样性相似。小非编码 RNA（例如 microRNA）是一类转录后调节因子，通过 3'UTR 中发现的基序发挥作用；然而，只有 3'UTR::microRNA 基序的一个子集是已知的。 MicroRNA 增强了先前已确立的已知调节表达的 RNA 结合蛋白的基本作用；然而，人们对这些蛋白质结合基序知之甚少。线虫提供了一个出色的模型来揭示 DNA 编码的功能元件，这些元件在基因组已完全绘制且 3'UTR 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，结合使用体外、体内和计算机方法来识别大部分或全部 3'UTR 及其中的功能序列元件。具体来说，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'UTR；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、Yeast-3-Hybrid 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，我们需要构建可能影响每个基因活性的 DNA 元素图谱。我们建议使用模型动物线虫来构建此类图谱的关键部分，方法是识别所有 3'UTR（调节基因表达的序列元件），并剖析 3'UTR 并识别负责 3'UTR 功能的子元件。

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.