UMMS Affiliation

Program in Molecular Medicine; RNA Therapeutics Institute

Publication Date

1-15-2017

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.

Rights and Permissions

Copyright 2017 Sherrard et al. Freely available online through the Genes and Development Open Access option. Citation: Genes Dev. 2017 Jan 15;31(2):209-222. Epub 2017 Feb 6. Link to article on publisher's site

DOI of Published Version

10.1101/gad.288555.116

Related Resources

Link to Article in PubMed

Keywords

BH3-only, C. elegans, development, embryo, miRNA, programmed cell death

Journal/Book/Conference Title

Genes and development

PubMed ID

28167500

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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