Our modENCODE parent grant U01-HG004261 is aimed at annotating the functional short regulatory RNAs of Drosophila melanogaster using deep sequencing methodology. These include known classes of Argonaute-bound RNA such as microRNAs, small interfering RNAs, and piRNAs. In addition, potentially novel classes of RNAs may be uncovered as a result of this project. We request administrative supplemental funding to expand the range of our efforts to discover and annotate novel transcripts that represent or generate short regulatory RNAs in Drosophila. The bulk of the requested funds are dedicated to 50% salary support of a new bioinformatician to perform essential analyses of the large amount of small RNA data that we have produced for the consortium. We hope to uncover edited RNAs and species with untemplated additions, and to analyze non-canonical genic sources of mi/si/piRNAs. The remainder of the funds will be devoted towards novel methods for constructing and sequencing libraries that are enriched for normally labile primary microRNA transcripts. Their analysis should not only help to define microRNA gene structures, but may prove to reveal novel types of normally labile transcripts that might escape conventional RNA-seq efforts. U01-HG004261-03S1 Lai ARRA supplement

Public Health Relevance

Small noncoding RNAs mediate broad regulatory networks that encompass most genes, including most protein-coding disease and cancer genes. A thorough annotation of small noncoding RNAs is necessary to fully catalog the genic content of the genome. Their identification is not only a basis for studies of novel drivers of disease, a better understanding of small RNA pathways will help efforts to exploit them to control gene expression for experimental and therapeutic uses.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01HG004261-03S1
Application #
7929797
Study Section
Special Emphasis Panel (ZHG1-HGR-P (J1))
Program Officer
Good, Peter J
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2011-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$168,861
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Wen, Jiayu; Mohammed, Jaaved; Bortolamiol-Becet, Diane et al. (2014) Diversity of miRNAs, siRNAs, and piRNAs across 25 Drosophila cell lines. Genome Res 24:1236-50
Gerstein, Mark B; Rozowsky, Joel; Yan, Koon-Kiu et al. (2014) Comparative analysis of the transcriptome across distant species. Nature 512:445-8
Brown, James B; Boley, Nathan; Eisman, Robert et al. (2014) Diversity and dynamics of the Drosophila transcriptome. Nature 512:393-9
Mohammed, Jaaved; Flynt, Alex S; Siepel, Adam et al. (2013) The impact of age, biogenesis, and genomic clustering on Drosophila microRNA evolution. RNA 19:1295-308
Ladewig, Erik; Okamura, Katsutomo; Flynt, Alex S et al. (2012) Discovery of hundreds of mirtrons in mouse and human small RNA data. Genome Res 22:1634-45
Westholm, Jakub O; Ladewig, Erik; Okamura, Katsutomo et al. (2012) Common and distinct patterns of terminal modifications to mirtrons and canonical microRNAs. RNA 18:177-92
Bejarano, Fernando; Bortolamiol-Becet, Diane; Dai, Qi et al. (2012) A genome-wide transgenic resource for conditional expression of Drosophila microRNAs. Development 139:2821-31
Smibert, Peter; Miura, Pedro; Westholm, Jakub O et al. (2012) Global patterns of tissue-specific alternative polyadenylation in Drosophila. Cell Rep 1:277-89
Axtell, Michael J; Westholm, Jakub O; Lai, Eric C (2011) Vive la différence: biogenesis and evolution of microRNAs in plants and animals. Genome Biol 12:221
Chung, Wei-Jen; Agius, Phaedra; Westholm, Jakub O et al. (2011) Computational and experimental identification of mirtrons in Drosophila melanogaster and Caenorhabditis elegans. Genome Res 21:286-300

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