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 el...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2014-12, Vol.3, p.e04265-e04265
Main Authors: Weaver, Benjamin P, Zabinsky, Rebecca, Weaver, Yi M, Lee, Eui Seung, Xue, Ding, Han, Min
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis
Apoptosis - genetics
Caenorhabditis elegans - cytology
Caenorhabditis elegans - embryology
Caenorhabditis elegans - genetics
Caenorhabditis elegans Proteins - chemistry
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Caspase
Caspases - genetics
Caspases - metabolism
Cell Lineage - genetics
Cooperation
Defects
Developmental biology
Developmental Biology and Stem Cells
DIS3L2
Embryonic Development - genetics
Enhancer Elements, Genetic - genetics
Gene expression
Gene Expression Regulation, Developmental
Genetic Pleiotropy
Genome
Genomes
GW182
heterochronic
Humans
Laboratories
Larva - metabolism
LIN28
MicroRNAs - metabolism
miRNA
Models, Biological
Molecular Sequence Data
Mutation
Phenotype
Physiology
Pleiotropy
Pluripotency
Pluripotent Stem Cells - metabolism
Proteasomes
Proteolysis
RNA Interference
RNA-Induced Silencing Complex
Signal Transduction - genetics
Stem cells
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.04265