Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein
Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein
In plants and invertebrates, viral-derived siRNAs processed by the RNaseIII Dicer guide Argonaute (AGO) proteins as part of antiviral RNA-induced silencing complexes (RISC). As a counterdefense, viruses produce suppressor proteins (VSRs) that inhibit the host silencing machinery, but their mechanisms of action and cellular targets remain largely unknown. Here, we show that the Turnip crinckle virus (TCV) capsid, the P38 protein, acts as a homodimer, or multiples thereof, to mimic host-encoded glycine/tryptophane (GW)-containing proteins normally required for RISC assembly/function in diverse organisms. The P38 GW residues bind directly and specifically to Arabidopsis AGO1, which, in addition to its role in endogenous microRNA-mediated silencing, is identified as a major effector of TCV-derived siRNAs. Point mutations in the P38 GW residues are sufficient to abolish TCV virulence, which is restored in Arabidopsis ago1 hypomorphic mutants, uncovering both physical and genetic interactions between the two proteins. We further show how AGO1 quenching by P38 profoundly impacts the cellular availability of the four Arabidopsis Dicers, uncovering an AGO1-dependent, homeostatic network that functionally connects these factors together. The likely widespread occurrence and expected consequences of GW protein mimicry on host silencing pathways are discussed in the context of innate and adaptive immunity in plants and metazoans.
Ribonuclease III, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Cell Cycle Proteins, MESH: Amino Acid Sequence, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, MESH: Plant Diseases, MESH: Argonaute Proteins, MESH: Ribonuclease III, Homeostasis, MESH: Gene Silencing, RNA, Small Interfering, MESH: Capsid Proteins, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Phylogenetics and taxonomy, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Molecular Biology/Molecular biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, MESH: Homeostasis, Argonaute Proteins, Host-Pathogen Interactions, Carmovirus, MESH: Carmovirus, Protein Binding, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, 570, MESH: Mutation, Molecular Biology/Biochemistry [q-bio.BM], Molecular Sequence Data, MESH: Sequence Alignment, MESH: Arabidopsis Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Small Interfering, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, MESH: Cell Cycle Proteins, MESH: RNA, MESH: Protein Binding, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Amino Acid Sequence, Gene Silencing, Molecular Biology, Plant Diseases, 580, [SDV.GEN]Life Sciences [q-bio]/Genetics, Molecular Biology/Genomics [q-bio.GN], MESH: Molecular Sequence Data, Molecular Biology/Structural Biology [q-bio.BM], Arabidopsis Proteins, MESH: Host-Pathogen Interactions, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Mutation, Capsid Proteins, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Sequence Alignment
Ribonuclease III, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Cell Cycle Proteins, MESH: Amino Acid Sequence, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, MESH: Plant Diseases, MESH: Argonaute Proteins, MESH: Ribonuclease III, Homeostasis, MESH: Gene Silencing, RNA, Small Interfering, MESH: Capsid Proteins, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Phylogenetics and taxonomy, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Molecular Biology/Molecular biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, MESH: Homeostasis, Argonaute Proteins, Host-Pathogen Interactions, Carmovirus, MESH: Carmovirus, Protein Binding, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, 570, MESH: Mutation, Molecular Biology/Biochemistry [q-bio.BM], Molecular Sequence Data, MESH: Sequence Alignment, MESH: Arabidopsis Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Small Interfering, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, MESH: Cell Cycle Proteins, MESH: RNA, MESH: Protein Binding, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Amino Acid Sequence, Gene Silencing, Molecular Biology, Plant Diseases, 580, [SDV.GEN]Life Sciences [q-bio]/Genetics, Molecular Biology/Genomics [q-bio.GN], MESH: Molecular Sequence Data, Molecular Biology/Structural Biology [q-bio.BM], Arabidopsis Proteins, MESH: Host-Pathogen Interactions, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Mutation, Capsid Proteins, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Sequence Alignment
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