UMMS Affiliation
Program in Molecular Medicine; RNA Therapeutics Institute
Publication Date
2017-01-15
Document Type
Article
Disciplines
Cell Biology | Developmental Biology
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.
Keywords
BH3-only, C. elegans, development, embryo, miRNA, programmed cell death
Rights and Permissions
Copyright 2017 Sherrard et al. Freely available online through the Genes and Development Open Access option.
DOI of Published Version
10.1101/gad.288555.116
Source
Genes Dev. 2017 Jan 15;31(2):209-222. Epub 2017 Feb 6. Link to article on publisher's site
Journal/Book/Conference Title
Genes and development
Related Resources
PubMed ID
28167500
Repository Citation
Sherrard, Ryan; Luehr, Sebastian; Holzkamp, Heinke; McJunkin, Katherine; Memar, Nadin; and Conradt, Barbara, "miRNAs cooperate in apoptosis regulation during C. elegans development" (2017). Open Access Articles. 3065.
https://escholarship.umassmed.edu/oapubs/3065
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.