期刊
GENES & DEVELOPMENT
卷 31, 期 2, 页码 209-222出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.288555.116
关键词
miRNA; programmed cell death; BH3-only; development; embryo; C. elegans
资金
- National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Charles King Trust Post-doctoral Research Fellowship
- National Institutes of Health [F32 GM097895, K99 GM113063-01, R01 GM069950]
- Deutsche Forschungsgemeinschaft (Center for Integrated Protein Science Munich [CIPSM] [EXC 114, SFB646]
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 bothmRNA 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 lineagespecific 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.
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