A recently discovered layer of gene regulation in eukaryotic organisms employs small regulatory RNAs (miRNAs and siRNAs). These RNAs are 20-28 nucleotides long and are produced by Dicer ribonucleases acting on double-stranded RNA precursors. Together with an effector protein complex, they scan for complementary RNA or DNA so that expression of these targeted molecules is silenced at the transcriptional or posttranscriptional levels. These short RNAs influence gene expression during growth and development and initiate epigenetic changes to DNA and chromatin. SIROCCO will characterize the full complement of miRNAs and siRNAs in animals and plants. Using bioinformatics, genomics, biochemistry, cell biology and genetics, the sortium members will reveal how these RNAs are produced and processed, how they are transported and how they target specific genes and RNAs for silencing. SIROCCO will investigate the miRNA and siRNA profiles associated with development, with phenotypic divergence within populations, and with diseased states including cancer. The functional genomics of silencing RNAs will be addressed by up- or down-regulation of miRNA and siRNA species. There will also be an assessment of miRNA and siRNA regulatory networks and their interaction with other cellular trol mechanisms.
The outputs of SIROCCO will include databases of silencing RNA sequence and function in several organisms, new technologies for detection and manipulation of these RNAs, and information that will allow siRNA and miRNA profiles to be used as molecular markers and diagnostic methods for natural biological variation including the perturbations associated with disease. SIROCCO will also identify potential targets of disease therapy amongst the components of the small RNA silencing systems.
Finally, insights generated in SIROCCO will improve the specificity with which small RNAs can be employed as therapeutic tools.
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Funding SchemeIP - Integrated Project