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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...

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Autores principales: Sherrard, Ryan, Luehr, Sebastian, Holzkamp, Heinke, McJunkin, Katherine, Memar, Nadin, Conradt, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
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.
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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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