Cargando…
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597506/ https://www.ncbi.nlm.nih.gov/pubmed/23516374 http://dx.doi.org/10.1371/journal.pgen.1003353 |
_version_ | 1782262637023723520 |
---|---|
author | Hunter, Shaun E. Finnegan, Emily F. Zisoulis, Dimitrios G. Lovci, Michael T. Melnik-Martinez, Katya V. Yeo, Gene W. Pasquinelli, Amy E. |
author_facet | Hunter, Shaun E. Finnegan, Emily F. Zisoulis, Dimitrios G. Lovci, Michael T. Melnik-Martinez, Katya V. Yeo, Gene W. Pasquinelli, Amy E. |
author_sort | Hunter, Shaun E. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3597506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35975062013-03-20 Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans Hunter, Shaun E. Finnegan, Emily F. Zisoulis, Dimitrios G. Lovci, Michael T. Melnik-Martinez, Katya V. Yeo, Gene W. Pasquinelli, Amy E. PLoS Genet Research Article 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. Public Library of Science 2013-03-14 /pmc/articles/PMC3597506/ /pubmed/23516374 http://dx.doi.org/10.1371/journal.pgen.1003353 Text en © 2013 Hunter et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Hunter, Shaun E. Finnegan, Emily F. Zisoulis, Dimitrios G. Lovci, Michael T. Melnik-Martinez, Katya V. Yeo, Gene W. Pasquinelli, Amy E. Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597506/ https://www.ncbi.nlm.nih.gov/pubmed/23516374 http://dx.doi.org/10.1371/journal.pgen.1003353 |
work_keys_str_mv | AT huntershaune functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans AT finneganemilyf functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans AT zisoulisdimitriosg functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans AT lovcimichaelt functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans AT melnikmartinezkatyav functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans AT yeogenew functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans AT pasquinelliamye functionalgenomicanalysisofthelet7regulatorynetworkincaenorhabditiselegans |