Reference - Detail
|Author||Weaver BP, Zabinsky R, Weaver YM, Lee ES, Xue D, Han M.|
|Title||CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans.|
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.
|MeSH||Amino Acid Sequence Animals Apoptosis / genetics* Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caspases / genetics Caspases / metabolism* Cell Lineage / genetics Embryonic Development / genetics* Enhancer Elements, Genetic / genetics Gene Expression Regulation, Developmental* Genetic Pleiotropy Genome Humans Larva / metabolism MicroRNAs / metabolism* Models, Biological Molecular Sequence Data Phenotype Pluripotent Stem Cells / metabolism RNA Interference RNA-Induced Silencing Complex Signal Transduction / genetics Time Factors|
|C.elegans||tm2432 tm3681 tm0918 tm1983 tm2573 tm3144 tm3228 tm3532 tm4344 tm5127 tm5169 tm5279 tm5312 tm760 tm770|