Sherrard, R;
Luehr, S;
Holzkamp, H;
McJunkin, K;
Memar, N;
Conradt, B;
(2017)
miRNAs cooperate in apoptosis regulation during C. elegans development.
Genes & Development
, 31
(2)
pp. 209-222.
10.1101/gad.288555.116.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | miRNAs cooperate in apoptosis regulation during C. elegans development |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/gad.288555.116 |
| Publisher version: | https://doi.org/10.1101/gad.288555.116 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, Developmental Biology, Genetics & Heredity, miRNA, programmed cell death, BH3-only, development, embryo, C. elegans, PROGRAMMED CELL-DEATH, NEMATODE CAENORHABDITIS-ELEGANS, ANIMAL DEVELOPMENT, PROAPOPTOTIC GENE, MICRORNA FAMILY, ACTIVATOR GENE, PROTEIN, EGL-1, PATHWAYS, IDENTIFICATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10070327 |
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