MicroRNAs: A Small Contribution from Worms
Amy E. Pasquinelli
University of California, San Diego

Since the recent emergence of microRNAs (miRNAs) as a new class of regulatory RNAs, rapid progress has been made in identifying new members of this class and in determining factors important for their expression and function. However, the mechanism by which these regulatory RNAs inhibit the expression of specific target messenger RNAs (mRNAs) is still unclear. My lab primarily focuses on the founding miRNA genes, lin-4 and let-7, and their genetically defined targets in the nematode C. elegans to understand how these miRNAs control development of the animal. The majority of animal miRNAs, including lin-4 and let-7, recognize sites of partial complementarity in the 3' untranslated regions (UTRs) of target genes, and this is believed to result in translational repression. Recently my lab demonstrated that regulation by lin-4 and let-7 in C. elegans also results in degradation of their mRNA targets. Currently, we are exploring the generality of mRNA degradation as an outcome of regulation by miRNAs. We are also attempting to identify the mRNA degradation intermediates and the protein factors that participate in this mechanism of regulation by miRNAs. Studying miRNAs and their targets in C. elegans allows us to analyze the effect of authentic mutants in miRNA genes on endogenous gene expression. By elucidating the function of miRNAs in this organism, we hope to contribute to the general understanding of this newly discovered and widely conserved mode of gene regulation.

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