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

Link to Article in PubMed

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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