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© 2013 Hunter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hunter SE, Finnegan EF, Zisoulis DG, Lovci MT, Melnik-Martinez KV, et al. (2013) Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans. PLoS Genet 9(3): e1003353. doi:10.1371/journal.pgen.1003353

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.

Details

Title
Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans
Author
Hunter, Shaun E; Finnegan, Emily F; Zisoulis, Dimitrios G; Lovci, Michael T; Melnik-Martinez, Katya V; Yeo, Gene W; Pasquinelli, Amy E
Section
Research Article
Publication year
2013
Publication date
Mar 2013
Publisher
Public Library of Science
ISSN
15537390
e-ISSN
15537404
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1327764008
Copyright
© 2013 Hunter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hunter SE, Finnegan EF, Zisoulis DG, Lovci MT, Melnik-Martinez KV, et al. (2013) Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans. PLoS Genet 9(3): e1003353. doi:10.1371/journal.pgen.1003353