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- Title
Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans.
- Authors
Hunter, Shaun E.; Finnegan, Emily F.; Zisoulis, Dimitrios G.; Lovci, Michael T.; Melnik-Martinez, Katya V.; Yeo, Gene W.; Pasquinelli, Amy E.
- Abstract
The let-7 microRNA (miRNA) regulates cellular differentiation across many animal species. Loss of let-7 activity causes abnormal development in Caenorhabditis elegans and unchecked cellular proliferation in human cells, which contributes to tumorigenesis. These defects are due to improper expression of protein-coding genes normally under let-7 regulation. While some direct targets of let-7 have been identified, the genome-wide effect of let-7 insufficiency in a developing animal has not been fully investigated. Here we report the results of molecular and genetic assays aimed at determining the global network of genes regulated by let-7 in C. elegans. By screening for mis-regulated genes that also contribute to let-7 mutant phenotypes, we derived a list of physiologically relevant potential targets of let-7 regulation. Twenty new suppressors of the rupturing vulva or extra seam cell division phenotypes characteristic of let-7 mutants emerged. Three of these genes, opt-2, prmt-1, and T27D12.1, were found to associate with Argonaute in a let-7-dependent manner and are likely novel direct targets of this miRNA. Overall, a complex network of genes with various activities is subject to let-7 regulation to coordinate developmental timing across tissues during worm development.
- Subjects
MICRORNA; CELL differentiation; ANIMAL species; CAENORHABDITIS elegans; CARCINOGENESIS
- Publication
PLoS Genetics, 2013, Vol 9, Issue 3, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1003353