: 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.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HG004276-04
Application #
7805616
Study Section
Special Emphasis Panel (ZHG1-HGR-P (J1))
Program Officer
Good, Peter J
Project Start
2007-05-04
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$376,857
Indirect Cost
Name
New York University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Weiser, Natasha E; Yang, Danny X; Feng, Suhua et al. (2017) MORC-1 Integrates Nuclear RNAi and Transgenerational Chromatin Architecture to Promote Germline Immortality. Dev Cell 41:408-423.e7
Gan, Hin Hark; Gunsalus, Kristin C (2015) Assembly and analysis of eukaryotic Argonaute-RNA complexes in microRNA-target recognition. Nucleic Acids Res 43:9613-25
Fernandez, Anita G; Mis, Emily K; Lai, Allison et al. (2014) Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans. G3 (Bethesda) 4:185-96
Gan, Hin Hark; Gunsalus, Kristin C (2013) Tertiary structure-based analysis of microRNA-target interactions. RNA 19:539-51
Fernandez, Anita G; Bargmann, Bastiaan O R; Mis, Emily K et al. (2012) High-throughput fluorescence-based isolation of live C. elegans larvae. Nat Protoc 7:1502-10
Gunsalus, Kristin C; Rhrissorrakrai, Kahn (2011) Networks in Caenorhabditis elegans. Curr Opin Genet Dev 21:787-98
Kiontke, Karin C; Felix, Marie-Anne; Ailion, Michael et al. (2011) A phylogeny and molecular barcodes for Caenorhabditis, with numerous new species from rotting fruits. BMC Evol Biol 11:339
Mangone, Marco; Manoharan, Arun Prasad; Thierry-Mieg, Danielle et al. (2010) The landscape of C. elegans 3'UTRs. Science 329:432-5
Fernandez, Anita G; Mis, Emily K; Bargmann, Bastiaan O R et al. (2010) Automated sorting of live C. elegans using laFACS. Nat Methods 7:417-8
Han, Ting; Manoharan, Arun Prasad; Harkins, Tim T et al. (2009) 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106:18674-9

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