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Isolation of Cognate RNA-protein Complexes from Cells Using Oligonucleotide-directed Elution
Published on: January 16, 2017
Post-transcriptional control of executioner caspases by RNA-binding proteins
Deni Subasic1,2, Thomas Stoeger1,3, Seline Eisenring1
1Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
Abstract:
Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3' untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3' UTRs in many metazoans, translational control of executioner caspases by RBPs might be a strategy used widely across the animal kingdom to control apoptosis.
Insights
RNA-binding proteins (RBPs) control apoptosis by repressing caspase translation in C. elegans. This post-transcriptional regulation ensures proper cell death control, with conserved mechanisms found in humans.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Caspases are crucial for apoptosis, with regulation occurring at multiple levels.
- Post-transcriptional control of caspases remains less understood.
- RNA-binding proteins (RBPs) play diverse roles in gene expression regulation.
Purpose of the Study:
- To investigate the role of RBPs in post-transcriptional regulation of caspases.
- To identify specific RBPs controlling caspase expression in C. elegans and humans.
- To elucidate the mechanisms of translational repression of caspases.
Main Methods:
- RNA-binding protein identification and characterization in C. elegans.
- Analysis of mRNA translation and 3' UTR binding sites.
- Investigation of caspase regulation in human cell lines.
Main Results:
- Four conserved RBPs (PUF-8, MEX-3, GLD-1, CGH-1) sequentially repress CED-3 caspase in C. elegans.
- GLD-1 represses CED-3 mRNA translation via its 3' UTR, providing dual apoptosis control.
- Homologs of these RBPs, including PUM1, QKI, and DDX6, regulate human caspase-3.
Conclusions:
- RBPs provide critical post-transcriptional control over executioner caspases.
- Translational repression of caspases by RBPs is a conserved mechanism for apoptosis regulation across metazoans.
- This finding highlights a widespread strategy for controlling programmed cell death.
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