CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans
- University of Colorado Boulder, United States
- Howard Hughes Medical Institute, University of Colorado Boulder, United States
Abstract
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 C. 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.
Article and author information
Author details
Reviewing Editor
- Leemor Joshua-Tor, Cold Spring Harbor Laboratory, United States
Version history
- Received: August 6, 2014
- Accepted: November 26, 2014
- Accepted Manuscript published: November 28, 2014 (version 1)
- Accepted Manuscript updated: December 3, 2014 (version 2)
- Version of Record published: December 30, 2014 (version 3)
Copyright
© 2014, Weaver et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans
eLife 3:e04265.
https://doi.org/10.7554/eLife.04265
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