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When Argonaute takes out the ribonuclease sword
1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA; Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
The Journal of Biological Chemistry
|November 29, 2023
Summary
Argonaute (AGO) proteins are essential for gene silencing across life. This review explores how AGO slicer activity, crucial for animal development, is activated and its relationship with GW182, revealing many unanswered questions.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Argonaute (AGO) proteins bind guide RNA/DNA to form complexes essential for gene regulation.
- All AGOs possess a PIWI domain with RNase H fold, suggesting an ancient endoribonuclease (slicer) ancestor.
- MicroRNA (miRNA)-mediated gene silencing in animals is often slicer-independent, yet slicer activity is vital for development.
Purpose of the Study:
- To highlight catalytic activation mechanism differences in slicing-competent AGOs.
- To elucidate the roles of metal ions in target recognition and cleavage by AGO proteins.
- To reevaluate target specificity of RNA-induced silencing complexes and explore the coevolution of slicer-independent regulation and GW182.
Main Methods:
- Literature review and synthesis of existing research on Argonaute proteins.
- Analysis of catalytic mechanisms and metal ion involvement in AGO-mediated cleavage.
- Exploration of evolutionary relationships between gene silencing pathways.
Main Results:
- Distinctions in catalytic activation mechanisms among slicing-competent AGOs are identified.
- The roles of two metal ions in target recognition and cleavage are highlighted.
- The coevolutionary relationship between slicer-independent gene regulation and the AGO-binding protein GW182 is explored.
Conclusions:
- AGO slicer activity, while not always required for miRNA silencing, is indispensable for critical developmental events in vertebrates.
- Understanding AGO catalytic mechanisms and target specificity is crucial for deciphering gene regulation.
- Significant questions remain regarding the precise utilization of AGO slicing activity in biological processes.
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