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Genes Dev. 2017 Jan 15;31(2):209-222. doi: 10.1101/gad.288555.116. Epub 2017 Feb 6.

miRNAs cooperate in apoptosis regulation during C. elegans development.

Author information

1
Center for Integrated Protein Science Munich - CIPSM, Department Biology II, Ludwig-Maximilians-University Munich, Planegg-Martinsried 82152, Germany.
2
Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01606, USA.

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

PMID:
28167500
PMCID:
PMC5322734
DOI:
10.1101/gad.288555.116
[Indexed for MEDLINE]
Free PMC Article

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