: 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.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHG1-HGR-P (J1))
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Good, Peter J
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New York University
Schools of Arts and Sciences
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