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miRNAs cooperate in apoptosis regulation during C. elegans development
Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322734/ https://www.ncbi.nlm.nih.gov/pubmed/28167500 http://dx.doi.org/10.1101/gad.288555.116 |
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author | Sherrard, Ryan Luehr, Sebastian Holzkamp, Heinke McJunkin, Katherine Memar, Nadin Conradt, Barbara |
author_facet | Sherrard, Ryan Luehr, Sebastian Holzkamp, Heinke McJunkin, Katherine Memar, Nadin Conradt, Barbara |
author_sort | Sherrard, Ryan |
collection | PubMed |
description | Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encodes a proapoptotic BH3-only protein. In addition, we present evidence that repression of egl-1 is dependent on binding sites for miR-35 and miR-58 family miRNAs within the egl-1 3′ untranslated region (UTR), which affect both mRNA copy number and translation. Furthermore, using single-molecule RNA fluorescent in situ hybridization (smRNA FISH), we show that egl-1 is transcribed in the mother of a cell programmed to die and that miR-35 and miR-58 family miRNAs prevent this mother from dying by keeping the copy number of egl-1 mRNA below a critical threshold. Finally, miR-35 and miR-58 family miRNAs can also dampen the transcriptional boost of egl-1 that occurs specifically in a daughter cell that is programmed to die. We propose that miRNAs compensate for lineage-specific differences in egl-1 transcriptional activation, thus ensuring that EGL-1 activity reaches the threshold necessary to trigger death only in daughter cells that are programmed to die. |
format | Online Article Text |
id | pubmed-5322734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53227342017-03-08 miRNAs cooperate in apoptosis regulation during C. elegans development Sherrard, Ryan Luehr, Sebastian Holzkamp, Heinke McJunkin, Katherine Memar, Nadin Conradt, Barbara Genes Dev Research Paper Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encodes a proapoptotic BH3-only protein. In addition, we present evidence that repression of egl-1 is dependent on binding sites for miR-35 and miR-58 family miRNAs within the egl-1 3′ untranslated region (UTR), which affect both mRNA copy number and translation. Furthermore, using single-molecule RNA fluorescent in situ hybridization (smRNA FISH), we show that egl-1 is transcribed in the mother of a cell programmed to die and that miR-35 and miR-58 family miRNAs prevent this mother from dying by keeping the copy number of egl-1 mRNA below a critical threshold. Finally, miR-35 and miR-58 family miRNAs can also dampen the transcriptional boost of egl-1 that occurs specifically in a daughter cell that is programmed to die. We propose that miRNAs compensate for lineage-specific differences in egl-1 transcriptional activation, thus ensuring that EGL-1 activity reaches the threshold necessary to trigger death only in daughter cells that are programmed to die. Cold Spring Harbor Laboratory Press 2017-01-15 /pmc/articles/PMC5322734/ /pubmed/28167500 http://dx.doi.org/10.1101/gad.288555.116 Text en © 2017 Sherrard et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Paper Sherrard, Ryan Luehr, Sebastian Holzkamp, Heinke McJunkin, Katherine Memar, Nadin Conradt, Barbara miRNAs cooperate in apoptosis regulation during C. elegans development |
title | miRNAs cooperate in apoptosis regulation during C. elegans development |
title_full | miRNAs cooperate in apoptosis regulation during C. elegans development |
title_fullStr | miRNAs cooperate in apoptosis regulation during C. elegans development |
title_full_unstemmed | miRNAs cooperate in apoptosis regulation during C. elegans development |
title_short | miRNAs cooperate in apoptosis regulation during C. elegans development |
title_sort | mirnas cooperate in apoptosis regulation during c. elegans development |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322734/ https://www.ncbi.nlm.nih.gov/pubmed/28167500 http://dx.doi.org/10.1101/gad.288555.116 |
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