1. RNase III nucleases from diverse kingdoms serve as antiviral effectors
- Author
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David H. Sachs, Sonja Schmid, Jean-Pierre Levraud, Leah R. Sabin, Lauren C. Aguado, Sara Cherry, Daniel Blanco-Melo, Maryline Panis, Jared May, Jaehee V. Shim, Benjamin R. tenOever, and Anne E. Simon
- Subjects
0301 basic medicine ,Ribonuclease III ,Virus Replication ,Antiviral Agents ,Article ,Evolution, Molecular ,03 medical and health sciences ,chemistry.chemical_compound ,Protein Domains ,Interferon ,RNA interference ,medicine ,Animals ,Humans ,RNA Viruses ,Polymerase ,Drosha ,Genetics ,Multidisciplinary ,biology ,RNA ,RNA-Dependent RNA Polymerase ,030104 developmental biology ,chemistry ,Viral replication ,biology.protein ,Nucleic Acid Conformation ,RNA, Viral ,DNA ,medicine.drug - Abstract
In contrast to the DNA-based viruses in prokaryotes, the emergence of eukaryotes provided the necessary compartmentalization and membranous environment for RNA viruses to flourish, creating the need for an RNA-targeting antiviral system1,2. Present day eukaryotes employ at least two main defense strategies that emerged as a result of this viral shift, namely antiviral RNA interference (RNAi) and the interferon (IFN) system2. Here, we demonstrate that Drosha and related RNase III ribonucleases from all three domains of life, also elicit RNA-targeting antiviral activity. Systemic evolution of ligands by exponential enrichment (SELEX) on this class of proteins illustrates the recognition of unbranched RNA stem loops. Biochemical analyses reveal that in this context, Drosha functions as an antiviral clamp, conferring steric hindrance on the RNA dependent RNA polymerases (RdRps) of diverse positive stranded RNA viruses. We present evidence for cytoplasmic translocation of RNase III nucleases in response to virus in diverse eukaryotes including: plants, arthropods, invertebrate chordates, and fish. These data implicate RNase III recognition of viral RNA as an antiviral defense that is independent of, and possibly predates, other known eukaryotic antiviral systems.
- Published
- 2017