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Functional genomic analysis of the let-7 regulatory network reveals novel targets with roles in growth and development

  • Author(s): Hunter, Shaun Edward
  • et al.
Abstract

Maintaining the proper balance between cellular proliferation and differentiation is essential to the success of multicellular organisms. Loss of regulation of these processes leads to disease states, such as cancer. The microRNA let-7 is a conserved regulatory gene that plays an important role in promoting differentiation. I have under taken a new approach to find novel regulatory targets of this essential gene in the C. elegans model system. I utilized the expression differences in wild-type and let-7 mutant strains to find candidate genes that are over-expressed in let-7 mutants. Filtering this population of genes with computational and other expression data yielded a list of potential target genes that I screened for functional interaction with let-7 by RNA interference. Among the interacting genes were several developmental regulators, some of which have conserved roles in regulating proliferation and differentiation in mammals, supporting a role for let-7 as a master regulator of these processes. I have also made significant progress toward developing a let-7 regulated reporter system that can be used to test for direct interactions with let-7 and also explore the target recognition rules for microRNAs in general

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