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Tools for studying and using small RNAs: from pathways to functions to therapies
Poster Title: Tools for studying and using small RNAs: from pathways to functions to therapies
Submitted on 29 Jun 2015
Author(s): Kenneth Chang and Gregory J. Hannon
Affiliations: Cold Spring Harbor Laboratory, Watson School of Biological Sciences
Poster Views: 1,206
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Poster Information
Abstract: During the past decade, small RNAs have emerged as crucial regulators of gene expression and genome function, having roles in almost every aspect of biology. Many small RNAs act through RNA interference (RNAi)-related mechanisms, which involve programming the RNA-induced silencing complex (RISC) to recognize and repress targets. One class of small RNA, the microRNAs (miRNAs), naturally regulates programmes of gene expression. Altered miRNA function contributes to human disease, and manipulation of specific miRNAs is now being pursued as a novel therapeutic modality. Small RNAs have also been adapted for use as tools based on reprogramming the RNAi machinery to silence specific coding or non-coding RNAs. These tools have been exploited to investigate gene function in cultured cells and in living animals. Genome-scale collections of silencing triggers permit phenotype-based genetic screens to be carried out easily in organisms in which they were previously difficult or impossible. Such strategies are being used to discover and validate new therapeutic targets, and small RNAs themselves may offer a mechanism for inhibiting targets that are currently viewed as 'undruggable'.Summary: This poster provides an overview of the tools that have been developed to understand the functions of small RNAs and, conversely, the use of small RNAs as tools. Tools that are based on small RNAs have been exploited to investigate gene function in cultured cells and in living animals. Small RNA biogenesis, discovery and functional roles are explored in detail. Screening approaches to functional genomics, in vivo methods and potential therapeutic applications are discussed.References: 1. Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nature Rev. Genet. 10, 94-108 (2009)
2. Griffiths-Jones, S. et al. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140—D144 (2006)
3. Lewis, B. P. et al. Prediction of mammalian microRNA targets. Cell 115, 787-798 (2003)
4. Sethupathy, P. et al. A guide through present computational approaches for the identification of mammalian microRNA targets. Nature Methods 3, 881-886 (2006)
5. Chi, S. W. et al. Argonauts HITS-CLIP decodes microRNA—mRNA Interaction maps. Nature 460, 479-486 (2009)
6. Karginov, F. V. et al. A biochemical approach to identifying microRNA targets. Proc. Natl Acad. Scl. USA 104, 19291-19296 (2007)
7. Orom, U. A., Kauppinen, S. & Lund, A. H. LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 372, 137-141 (2006)
8. Meister, G. et al. Sequence-specific inhibition of microRNA- and siRNA-Induce
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