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CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans.

Benjamin P Weaver | Rebecca Zabinsky | Yi M Weaver | Eui Seung Lee | Ding Xue | Min Han
eLife | 2014

Genetic redundancy and pleiotropism have limited the discovery of functions associated with miRNAs and other regulatory mechanisms. To overcome this, we performed an enhancer screen for developmental defects caused by compromising both global miRISC function and individual genes in Caenorhabditis elegans. Among 126 interactors with miRNAs, we surprisingly found the CED-3 caspase that has only been well studied for its role in promoting apoptosis, mostly through protein activation. We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. Specifically, LIN-14, LIN-28, and DISL-2 proteins are known miRNA targets, key regulators of developmental timing, and/or stem cell pluripotency factors involved in miRNA processing. We show CED-3 cleaves these proteins in vitro. We also show CED-3 down-regulates LIN-28 in vivo, possibly rendering it more susceptible to proteasomal degradation. This mechanism may critically contribute to the robustness of gene expression dynamics governing proper developmental control.

Pubmed ID: 25432023

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM047869
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM059083
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008759
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIGMS NIH HHS, United States
    Id: 2T32GM008759-11
  • Agency: NIGMS NIH HHS, United States
    Id: 5R01GM047869
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM059083
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM142607

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Cold Spring Harbor Laboratory (tool)

RRID:SCR_008326

Non profit, private research and education institution that performs molecular and genetic research used to generate methods for better diagnostics and treatments for cancer and neurological diseases. Research of cancer causing genes and their respective signaling pathways, mutations and structural variations of the human genome that could cause neurodevelopmental and neurodegenerative illnesses such as autism, schizophrenia, and Alzheimer's and Parkinson's diseases and also research in plant genetics and quantitative biology.

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TargetScan (tool)

RRID:SCR_010845

Web tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.

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Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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