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RNA interference and other cell-autonomous defenses IFN-induced - - PowerPoint PPT Presentation
RNA interference and other cell-autonomous defenses IFN-induced - - PowerPoint PPT Presentation
RNA interference and other cell-autonomous defenses IFN-induced antiviral mediators / IFN system as well as many IFN-induced antiviral mediators are absent in plants What constitutes antiviral response in plants (nematodes and insects)? RNA
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RNA interference http://www.nature.com/focus/rnai/animations/
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- C. elegance
Drosophila Arabidopsis thaliana
Players of today’s lecture
Vertebrates
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siRNAs miRNAs (siRNAs)
Types of dsRNAs
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Insect antiviral system
Major steps and mediators of si/miRNA pathways
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Dicer family Evolution of si/miRNA pathway Substrate specificity of Dicers Arabidopsis
DCL1; -2; -3; -4 miRNA siRNA (22, 21, 24 nucleotides)
Drosophila
Dicer-1 miRNA siRNA Dicer-2
- C. elegant, vertebrates
Dicer-1 miRNA; siRNA
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Sources of dsRNAs
Plants and worms RNA-dependent RNA polymerases (RDRPs) Secondary siRNAs
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Transitivity (generation of secondary siRNAs)
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Dicer Products (mature dsRNAs)
monophosphate in primary siRNAs di- or triphosphates in secondary siRNAs
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Dicer Products (mature dsRNAs)
methylated
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Executor complex - RNA-induced silencing complex (RISC)
Multisubunit (multifunctional) complexes Argonaute (Ago) dsRNA-binding proteins (DRBs) Nucleases (dicers) Helicases … Drosophila (5 Ago) Ago-1 miRNA siRNA Ago-2
- C. elegans – 26; Arabidopsis - 10
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Inhibition of translation
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Inhibition of transcription
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Role of RNA interference in antiviral response
Evidence: Virus-derived (vi-siRNAs) accumulate during infections (plants) Viruses produce suppressors of RNA silencing (vSRS) siRNAs miRNAs (lsiRNAs?) Direct antiviral effect Indirect antiviral effect Inhibition of suppressors of various proteins of defense response
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siRNA mediated immunization
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siRNA mediated antiviral response (race for survival)
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Viral evasion of RNA silencing
Viruses (plant viruses) produce vSRS: sequestering dsRNAs (dsRNA-binding properties) inhibition of vi-dsRNA processing targeting 3’ methylation (stability of siRNAs is affected) competing with Ago for ssRNA binding binding Ago directly and preventing slicing targeting Ago (RISC) for degradation degradation of primary vi-dsRNAs inhibition of RDRP and generation of secondary vi-dsRNAs dsRNA spread? …
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Animal viruses: Use miRNA system for their advantage (HCV replication) Encode multiple vmiRNAs However: Encode vSRS proteins miRNAs (IFN-induced miRNAs) inhibit viral replication vi-miRNAs target cellular (or viral genes) for the inhibition Is RNA silencing involved in antiviral response in organisms other than plants?
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