Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans.
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3597506?pdf=render |
| _version_ | 1818360887307665408 |
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| author | Shaun E Hunter Emily F Finnegan Dimitrios G Zisoulis Michael T Lovci Katya V Melnik-Martinez Gene W Yeo Amy E Pasquinelli |
| author_facet | Shaun E Hunter Emily F Finnegan Dimitrios G Zisoulis Michael T Lovci Katya V Melnik-Martinez Gene W Yeo Amy E Pasquinelli |
| author_sort | Shaun E Hunter |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T21:07:56Z |
| format | Article |
| id | doaj.art-9e79cabe4df8400b9a6000926f1efd08 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-13T21:07:56Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-9e79cabe4df8400b9a6000926f1efd082022-12-21T23:31:25ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0193e100335310.1371/journal.pgen.1003353Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans.Shaun E HunterEmily F FinneganDimitrios G ZisoulisMichael T LovciKatya V Melnik-MartinezGene W YeoAmy E PasquinelliThe 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.http://europepmc.org/articles/PMC3597506?pdf=render |
| spellingShingle | Shaun E Hunter Emily F Finnegan Dimitrios G Zisoulis Michael T Lovci Katya V Melnik-Martinez Gene W Yeo Amy E Pasquinelli Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. PLoS Genetics |
| title | Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. |
| title_full | Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. |
| title_fullStr | Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. |
| title_full_unstemmed | Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. |
| title_short | Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. |
| title_sort | functional genomic analysis of the let 7 regulatory network in caenorhabditis elegans |
| url | http://europepmc.org/articles/PMC3597506?pdf=render |
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