GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

InterPro PAZ domain (IPR003100) predicts RNA binding
InterPro Piwi domain (IPR003165) predicts nucleic acid binding

GO_REF:0000033

Annotation inferences using phylogenetic trees

Phylogenetic inference from Argonaute family members
Some inferred functions may not apply to WAGO subfamily due to loss of catalytic residues

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

RNA-mediated gene silencing keyword mapped to GO terms

PMID:19800275

Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline.

WAGO-1 localizes to P granules in the germline

"We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules"
WAGO-1 binds 22G-RNAs (secondary siRNAs)

"Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes"
WAGO-1 silences transposons, pseudogenes, and cryptic loci

"WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci"
WAGO-1 is part of a genome surveillance system distinct from CSR-1 pathway

"We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1"
DRH-3 is required for 22G-RNA biogenesis

"DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems"

PMID:24684931

The Vasa Homolog RDE-12 engages target mRNA and multiple argonaute proteins to promote RNAi in C. elegans.

WAGO-1 physically interacts with RDE-12 (Vasa homolog DEAD-box helicase)

"These studies identified a robust association between WAGO-1 and a conserved Vasa ATPase-related protein RDE-12"
RDE-12 colocalizes with WAGO-1 in P granules

"RDE-12 colocalizes with WAGO-1 in germline P granules and in cytoplasmic and perinuclear foci in somatic cells"
RDE-12 is required for secondary siRNA production

"rde-12 mutants are deficient in RNAi, including viral suppression, and fail to produce amplified secondary siRNAs and certain endogenous siRNAs (endo-siRNAs)"
RDE-12 forms RNase-resistant complex with WAGO-1

"RDE-12 forms an RNase-resistant (target mRNA-independent) complex with WAGO-1"

PMID:17110334

Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.

WAGO subfamily Argonautes lack conserved metal-binding residues

"these AGO proteins lack key residues required for mRNA cleavage"
WAGO proteins probably do not cleave target mRNAs directly

"these AGO proteins lack key residues required for mRNA cleavage"
Distinct Argonautes act sequentially in RNAi pathway

"functionally and structurally distinct AGOs act sequentially to direct gene silencing"

PMID:29775580

ZNFX-1 Functions within Perinuclear Nuage to Balance Epigenetic Signals.

WAGO-1 interacts with ZNFX-1
ZNFX-1 functions in perinuclear nuage for epigenetic regulation

file:worm/wago-1/wago-1-deep-research-falcon.md

Falcon deep research report for C. elegans wago-1 (Q21770)

WAGO-1 is a worm-specific Argonaute (WAGO clade) that binds 22G-RNAs and acts as a cytoplasmic/perinuclear post-transcriptional effector in germline genome surveillance, consistent with the slicer-independent (non-catalytic) nature of WAGO-clade Argonautes.

"the best-supported assignment is **WAGO-1 as primarily a cytoplasmic/perinuclear post-transcriptional effector** within the WAGO 22G-RNA surveillance pathway"
WAGO-1 is classified within the 22G-RNA-binding WAGO group, together with silencing WAGOs (PPW-2/WAGO-3, HRDE-1/WAGO-9) that target silenced germline genes, pseudogenes, and repetitive/transposable elements.

"**WAGO-1** is classified within the **22G-RNA-binding WAGO group/cluster**, together with related silencing WAGOs (including PPW-2/WAGO-3 and HRDE-1/WAGO-9) that preferentially target **silenced germline genes, pseudogenes, and repetitive/transposable elements**"
WAGO-clade Argonautes lack the catalytic residues required for Slicer activity, so WAGO-1-mediated silencing occurs via cleavage-independent mechanisms (e.g., recruitment of RNA decay/silencing factors), supporting removal of intrinsic RNA endonuclease activity.

"WAGO-family Argonautes were reported to **lack the catalytic residues required for Slicer activity**, implying WAGO-mediated silencing often occurs via **cleavage-independent mechanisms**"
22G-RNAs are ~22-nt secondary siRNAs with a strong 5' guanosine bias, produced by RNA-dependent RNA polymerases and loaded onto WAGOs without Dicer processing.

"RdRP-produced 22G-RNAs can be loaded onto WAGOs “**without Dicer**” processing"
Transposon 22G-RNAs are enriched in WAGO-1 immunoprecipitation, and 22G-RNA biogenesis depends on a core module including DRH-3 and RdRPs (RRF-1/EGO-1) and EKL-1.

"Gu et al. show **transposon 22G-RNAs** are enriched in **WAGO-1 immunoprecipitation** samples"
WAGO-1 localizes to perinuclear germ granules, specifically P granules; Chen et al. (2024) explicitly position P-granule-localized CSR-1 and WAGO-1 within germ granule subcompartments.

"Chen et al. (2024) explicitly list **“P granule localized CSR-1 and WAGO-1”** in the context of germ granule subcompartment architecture"
WAGO-1 acts downstream of piRNA targeting: piRNA binding initiates secondary WAGO 22G-RNA production, with heritable nuclear silencing executed mainly by HRDE-1 rather than WAGO-1.

"piRNA binding initiates secondary WAGO 22G-RNA production"

file:worm/wago-1/wago-1-deep-research-openscientist.md

OpenScientist functional annotation report for C. elegans WAGO-1