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 R, Luehr S, Holzkamp H, McJunkin K, Memar N, Conradt B. (2017). miRNAs cooperate in apoptosis regulation during C. elegans development. Open Access Publications by UMMS Authors. https://doi.org/10.1101/gad.288555.116. Retrieved from https://escholarship.umassmed.edu/oapubs/3065
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.