Genome-wide expression profiling of miRNAs with single cell resolution
Principal Investigator: Oliver Hobert
Abstract: [unreadable] DESCRIPTION (provided by applicant): MicroRNAs are gene regulatory factors whose abundance (~1% of genes in animal genomes) has only recently become apparent. In spite of their abundance, little is known about their expression patterns and the physiological contexts in which they function. The few animal miRNAs that have been functionally studied to date suggest that miRNAs are embedded in gene regulatory cascades that determine cell fate specification. Moreover, it is conceivable that miRNAs may follow the precedent of transcription factors and act in a combinatorial manner, such that specific combinations of miRNAs expressed in a given cell type may define and actively determine the identity of the cell type. To substantiate this hypothesis, the investigator will determine miRNA expression profiles both on a genome-wide level as well as with a single cell resolution using the nematode C. elegans as a model system. His studies will (1) build a catalogue of miRNA expression profiles, (2) provide a guideline for future phenotypic analysis of miRNA knockouts, and (3) provide supportive evidence for the concept of "miRNA codes", and therefore supply further testable hypothesis about miRNA function in the generation of cellular diversity in a developing organism. Moreover, it will (4) validate the "sensor strategy" to determine miRNA expression profiles in C. elegans, and (5) build a toolkit of potentially useful gfp cell fate markers. [unreadable] [unreadable]
Funding Period: 2005-07-01 - 2008-06-30
more information: NIH RePORT
- Perfect seed pairing is not a generally reliable predictor for miRNA-target interactionsDominic Didiano
Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, Howard Hughes Medical Institute, 701 W 168th Street, New York, New York 10032, USA
Nat Struct Mol Biol 13:849-51. 2006..Rather, lsy-6 can functionally interact with its target site only in specific 3' UTR contexts. Our findings illustrate the difficulty of establishing generalizable rules of miRNA-target interactions...