Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
GOA annotations for C. elegans wago-4
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The fetched GOA line for the contested GO:0004521 IBA annotation
propagates RNA endonuclease activity through PANTHER:PTN008584027 and
a broad Argonaute source set.
"UniProtKB O62275 wago-4 enables GO:0004521 RNA endonuclease activity molecular_function ECO:0000318 IBA GO_REF:0000033 AGI_LocusCode:AT1G48410|AGI_LocusCode:AT2G27040|FB:FBgn0000146|FB:FBgn0004872|FB:FBgn0087035|FB:FBgn0250816|FB:FBgn0262739|MGI:MGI:1928897|MGI:MGI:1930036|MGI:MGI:2446632|PANTHER:PTN008584027|PomBase:SPCC736.11|UniProtKB:O67434|UniProtKB:Q9H9G7|UniProtKB:Q9UKV8|WB:WBGene00000105|WB:WBGene00000106|WB:WBGene00004323|WB:WBGene00017641 6239 Caenorhabditis elegans GO_Central Argonaute protein wago-4 20241120"
OpenScientist hypothesis investigation - WAGO-4 RNA endonuclease activity
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OpenScientist refuted the hypothesis that WAGO-4 directly has RNA
endonuclease activity.
"The hypothesis that *C. elegans* WAGO-4 (UniProt: O62275) possesses RNA endonuclease activity (GO:0004521) is **refuted**."
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OpenScientist found that WAGO-4 lacks three of the four catalytic
PIWI-domain tetrad positions required for Argonaute slicer activity.
"Two independent computational analyses confirm that WAGO-4 lacks the conserved DEDH catalytic tetrad at three of four critical positions in its PIWI domain"
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The report's motif-scanning result identifies the WAGO-4 non-conserved
D1, D2, and H catalytic-site equivalents.
"D1=G676 (score 31), D2=T756 (score 41), H=N913 (score 31) — non-conservative substitutions at three critical positions"
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.
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The downstream/secondary Argonautes of C. elegans (the WAGO clade, which includes WAGO-4/F58G1.1) act after the primary Argonaute RDE-1 and lack the catalytic residues required for target-mRNA cleavage.
"Interestingly, these AGO proteins lack key residues required for mRNA cleavage."
Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint.
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wago-4 (F58G1.1, allele tm1019) was tested only as one member of the six-gene MAGO secondary-Argonaute group whose collective loss impairs dsRNA-triggered H3K9me3 chromatin modification.
"MAGO (ppw-1(tm914), sago-1(tm1195), sago-2(tm894), F58G1.1(tm1019), C06A1.4(tm887), and M03D4.6(tm1144)]"
Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance.
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WAGO-4 is required for RNAi inheritance, physically associates with the helicase ZNFX-1, and with ZNFX-1 defines the Z granule, a liquid-like condensate between P granules and Mutator foci.
"Here we show that the inheritance factors ZNFX-1 and WAGO-4 localize to a liquid-like condensate that we name the Z granule."
A Cytoplasmic Argonaute Protein Promotes the Inheritance of RNAi.
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WAGO-4 is a cytoplasmic Argonaute required for RNAi inheritance that binds 22G-RNAs and their mRNA targets; its 22G-RNAs overlap the CSR-1 germline cohort and carry 3' untemplated uridylation.
"WAGO-4 binds to 22G-RNAs and their mRNA targets."
MINA-1 and WAGO-4 are part of regulatory network coordinating germ cell death and RNAi in C. elegans.
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WAGO-4 is a germline-specific Argonaute whose level is a dosage-sensitive positive determinant of RNAi (overexpression causes RNAi hypersensitivity), it co-precipitates with MINA-1, and it is a transient P-granule component.
"we found that the germline-specific Argonaute WAGO-4 protein levels are increased in mina-1 mutant background."