CSR-1 is a C. elegans Argonaute that binds endogenous 22G siRNAs and regulates complementary transcripts through RNA cleavage, translational repression, and protection from competing silencing pathways. It acts in cytoplasmic germ granules and at nuclear chromatin, contributes to proper chromosome segregation, and supports germline gene expression and fertility. The locus produces long CSR-1a (H2KZD5) and short CSR-1b (Q27GU1), sharing PAZ/PIWI domains and catalytic residues but differing in an N-terminal extension, expression, and guide-RNA targets. CSR-1b is broadly expressed in the germline and accounts for many previously characterized essential functions; CSR-1a has spermatogenic and somatic roles, including intestinal gene repression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000070 mitotic sister chromatid segregation | IMP PMID:17110334 Analysis of the C. elegans Argonaute family reveals that dis... | ACCEPT | Summary: mitotic sister chromatid segregation is supported for CSR-1. Reason: Retain the curated mutant-based chromosome segregation assertion. The 2006 source is abstract-only, but the independent 2009 target study demonstrates chromosome alignment/segregation defects and chromosome association of the CSR-1 pathway, corroborating biological participation rather than inferring a spindle enzyme. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. |
| GO:0000794 condensed nuclear chromosome | IDA PMID:19804758 The Argonaute CSR-1 and its 22G-RNA cofactors are required f... | ACCEPT | Summary: condensed nuclear chromosome is supported for CSR-1. Reason: Retain the curator-recorded localization from the CSR-1 chromosome study. Its abstract independently establishes chromosome association, target-locus chromatin association, and metaphase alignment defects; it does not reproduce every localization image. The exact IDA term is therefore retained with explicit full-text limitation rather than rejected from incomplete access. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. PMID:19804758 We show that CSR-1 interacts with chromatin at target loci |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | ACCEPT | Summary: nucleic acid binding is supported for CSR-1. Reason: CSR-1 physically associates with single-stranded antisense 22G-RNA guides and complementary target RNA. PAZ/PIWI architecture, target assays, and the actual positive PAINT lineage support the binding terms; broader nucleic-acid/RNA binding remains true and is not rejected solely for breadth. Supporting Evidence: PMID:19804758 the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. PMID:22863779 CSR-1 directly binds to histone mRNA in an ego-1-dependent manner |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: RNA binding is supported for CSR-1. Reason: CSR-1 physically associates with single-stranded antisense 22G-RNA guides and complementary target RNA. PAZ/PIWI architecture, target assays, and the actual positive PAINT lineage support the binding terms; broader nucleic-acid/RNA binding remains true and is not rejected solely for breadth. Supporting Evidence: PMID:19804758 the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. PMID:22863779 CSR-1 directly binds to histone mRNA in an ego-1-dependent manner |
| GO:0003727 single-stranded RNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: single-stranded RNA binding is supported for CSR-1. Reason: CSR-1 physically associates with single-stranded antisense 22G-RNA guides and complementary target RNA. PAZ/PIWI architecture, target assays, and the actual positive PAINT lineage support the binding terms; broader nucleic-acid/RNA binding remains true and is not rejected solely for breadth. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000527276 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:19804758 the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. PMID:22863779 CSR-1 directly binds to histone mRNA in an ego-1-dependent manner |
| GO:0004521 RNA endonuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: RNA endonuclease activity is supported for CSR-1. Reason: Aoki et al. directly attribute secondary-siRNA-guided target RNA slicing to CSR-1. This supports both the specific siRNA-paired endoribonuclease term and its general RNA-endonuclease ancestor. The inactive-Argonaute reasoning applicable to human AGO4 or some WAGOs does not apply to this experimentally active slicer; both CSR-1 isoforms retain the same catalytic tetrad. The cached Aoki article is abstract-only, but explicitly identifies the target and reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008584027 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:18007599 An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. PMID:34329465 both CSR-1 isoforms possess the same catalytic tetrad within the PIWI domain |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus is supported for CSR-1. Reason: Nuclear/chromatin localization is supported by target experimental annotations and the independent chromosome-associated CSR-1 study. Cytoplasmic and P-granule localization does not exclude the nuclear pool. Some individual source papers are abstract-only and do not reproduce the exact image, so retained IDA assertions are not claimed to have been independently image-verified. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001875625 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. PMID:19804758 We show that CSR-1 interacts with chromatin at target loci |
| GO:0005634 nucleus | IDA PMID:19804758 The Argonaute CSR-1 and its 22G-RNA cofactors are required f... | ACCEPT | Summary: nucleus is supported for CSR-1. Reason: Nuclear/chromatin localization is supported by target experimental annotations and the independent chromosome-associated CSR-1 study. Cytoplasmic and P-granule localization does not exclude the nuclear pool. Some individual source papers are abstract-only and do not reproduce the exact image, so retained IDA assertions are not claimed to have been independently image-verified. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. PMID:19804758 We show that CSR-1 interacts with chromatin at target loci |
| GO:0005634 nucleus | IDA PMID:22231398 A conserved PUF-Ago-eEF1A complex attenuates translation elo... | ACCEPT | Summary: nucleus is supported for CSR-1. Reason: Nuclear/chromatin localization is supported by target experimental annotations and the independent chromosome-associated CSR-1 study. Cytoplasmic and P-granule localization does not exclude the nuclear pool. Some individual source papers are abstract-only and do not reproduce the exact image, so retained IDA assertions are not claimed to have been independently image-verified. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. PMID:19804758 We show that CSR-1 interacts with chromatin at target loci |
| GO:0005634 nucleus | IDA PMID:22863779 CSR-1 RNAi pathway positively regulates histone expression i... | ACCEPT | Summary: nucleus is supported for CSR-1. Reason: Nuclear/chromatin localization is supported by target experimental annotations and the independent chromosome-associated CSR-1 study. Cytoplasmic and P-granule localization does not exclude the nuclear pool. Some individual source papers are abstract-only and do not reproduce the exact image, so retained IDA assertions are not claimed to have been independently image-verified. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. PMID:19804758 We show that CSR-1 interacts with chromatin at target loci |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm is supported for CSR-1. Reason: The actual PAINT ancestor supports cytoplasmic activity, and direct CSR-1 P-granule localization and target translational repression corroborate this compartment. Nuclear association is a complementary pool, not a reason to reject cytoplasm. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000527275 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:34244496 During L4, where both isoforms are expressed in the spermatogenesis region, CSR-1A and CSR-1B co-localize at P granules. PMID:22231398 the FBF-1-CSR-1 heterodimer inhibited EFT-3 (eEF1A) GTPase activity in vitro. |
| GO:0016442 RISC complex | IBA GO_REF:0000033 | ACCEPT | Summary: RISC complex is supported for CSR-1. Reason: Retain the inherited RISC-complex assignment: CSR-1 is a small-RNA-loaded Argonaute with directly demonstrated guide-dependent target cleavage and post-transcriptional repression. Its gene-licensing activities do not exclude an RNA-induced silencing complex in other contexts. The target is an actual descendant of the positive PTN001113179 node. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001113179 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:18007599 An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. file:worm/csr-1/csr-1-H2KZD5-paint-lineage.json PTN001113179 |
| GO:0035194 regulatory ncRNA-mediated post-transcriptional gene silencing | IBA GO_REF:0000033 | ACCEPT | Summary: regulatory ncRNA-mediated post-transcriptional gene silencing is supported for CSR-1. Reason: Direct CSR-1 secondary-siRNA-dependent target cleavage and translational-repression experiments support post-transcriptional silencing and, for the specific IDA row, cleavage-associated target destabilization. Positive licensing of other transcripts and the 2009 observation of unchanged abundance for tested chromosomal targets do not globally contradict this activity. Distinguish context and isoform; neither all CSR-1-bound RNAs nor every gene-regulatory role is silencing. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001113179 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:18007599 An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. PMID:18007599 Secondary rather than primary siRNAs may play a major role in the destabilization of target transcripts during RNAi in C. elegans. PMID:22231398 Nematode CSR-1 (Ago) promoted repression of FBF (PUF) target mRNAs in in vivo assays |
| GO:0035194 regulatory ncRNA-mediated post-transcriptional gene silencing | IMP PMID:17110334 Analysis of the C. elegans Argonaute family reveals that dis... | ACCEPT | Summary: regulatory ncRNA-mediated post-transcriptional gene silencing is supported for CSR-1. Reason: Direct CSR-1 secondary-siRNA-dependent target cleavage and translational-repression experiments support post-transcriptional silencing and, for the specific IDA row, cleavage-associated target destabilization. Positive licensing of other transcripts and the 2009 observation of unchanged abundance for tested chromosomal targets do not globally contradict this activity. Distinguish context and isoform; neither all CSR-1-bound RNAs nor every gene-regulatory role is silencing. Supporting Evidence: PMID:18007599 An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. PMID:18007599 Secondary rather than primary siRNAs may play a major role in the destabilization of target transcripts during RNAi in C. elegans. PMID:22231398 Nematode CSR-1 (Ago) promoted repression of FBF (PUF) target mRNAs in in vivo assays |
| GO:0035198 miRNA binding | IBA GO_REF:0000033 | UNDECIDED | Summary: The focused report confirms 22G guide specialization but does not establish loss of inherited miRNA binding. Reason: H2KZD5 leaf PTN000527417 genuinely descends from miRNA-binding IBD PTN001113179; the actual tree establishes ancestral support. CSR-1 IP and isoform-resolved studies identify selective 22G-siRNA complexes with different target pools, a concrete guide-specificity question. The focused OpenScientist report recovers these findings and confirms the corrected identities, but its removal/NOT recommendation relies on absent target miRNA assays and a family-versus-target distinction that does not refute an IBA. It explicitly states that the miRNA fraction was not quantified/excluded, uses PubMed abstracts, and did not dereference the target leaf. Its report and CSVs contain no binding-exclusion experiment or demonstrated target-path loss. Full PMID:34244496 methods use polyphosphatase-treated small-RNA libraries and gene-feature enrichment; the paper establishes relative 22G target specificity, not an isolated miRNA-loading prohibition. Retain UNDECIDED with curator/full-primary-data follow-up on physiological guide loading. Do not add NOT, treat transcript tuning as incompatible with all silencing, or add a redundant siRNA-binding NEW beneath existing RNA-binding assertions. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001113179 UNRESOLVED Actual target descent is established. The completed focused report supplies no demonstrated target-path loss or direct miRNA-binding exclusion; selective 22G guide recovery leaves the physiological capacity unresolved. Supporting Evidence: file:worm/csr-1/csr-1-H2KZD5-paint-lineage.json PTN001113179 PMID:19804758 the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. PMID:34329465 small RNA sequencing of CSR-1 complexes shows that they interact with partly overlapping sets of 22G-RNAs. PMID:34244496 multiple dimethylarginine modifications, which are necessary for the preferential binding of CSR-1A to spermatogenesis-specific 22G-RNAs. file:worm/csr-1/csr-1-hypotheses/corrected-argonaute-mirna-binding-specificity/openscientist.md Published IPs report 22G-RNAs; miRNA fraction not explicitly quantified/excluded |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasmic ribonucleoprotein granule is supported for CSR-1. Reason: Retain the cytoplasmic ribonucleoprotein-granule/P-granule localization. Gene-level microscopy is corroborated by isoform-resolved 2021 observations that both CSR-1 isoforms colocalize at P granules during spermatogenesis; no assumption of exclusive granule residence is made. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001113179 SUPPORTS TRANSFER Target descent is established in the actual PTHR22891 topology and target primary evidence corroborates the function/location. Supporting Evidence: PMID:34244496 During L4, where both isoforms are expressed in the spermatogenesis region, CSR-1A and CSR-1B co-localize at P granules. |
| GO:0043186 P granule | IDA PMID:19804758 The Argonaute CSR-1 and its 22G-RNA cofactors are required f... | ACCEPT | Summary: P granule is supported for CSR-1. Reason: Retain the cytoplasmic ribonucleoprotein-granule/P-granule localization. Gene-level microscopy is corroborated by isoform-resolved 2021 observations that both CSR-1 isoforms colocalize at P granules during spermatogenesis; no assumption of exclusive granule residence is made. Supporting Evidence: PMID:34244496 During L4, where both isoforms are expressed in the spermatogenesis region, CSR-1A and CSR-1B co-localize at P granules. |
| GO:0070090 metaphase plate | IDA PMID:19804758 The Argonaute CSR-1 and its 22G-RNA cofactors are required f... | ACCEPT | Summary: metaphase plate is supported for CSR-1. Reason: Retain the curator-recorded localization from the CSR-1 chromosome study. Its abstract independently establishes chromosome association, target-locus chromatin association, and metaphase alignment defects; it does not reproduce every localization image. The exact IDA term is therefore retained with explicit full-text limitation rather than rejected from incomplete access. These are gene-level CSR-1 observations; older experiments generally did not distinguish isoforms. The representative H2KZD5 accession is CSR-1a, while later isoform-resolved work assigns many constitutive germline/embryonic functions to CSR-1b (Q27GU1). Preserve the GOA assertion without relabeling the older assay as isoform-a-specific. Supporting Evidence: PMID:19804758 localize to chromosomes and are required for proper chromosome segregation. PMID:19804758 We show that CSR-1 interacts with chromatin at target loci |
| GO:0070551 endoribonuclease activity, cleaving siRNA-paired mRNA | IDA PMID:18007599 In vitro analyses of the production and activity of secondar... | ACCEPT | Summary: endoribonuclease activity, cleaving siRNA-paired mRNA is supported for CSR-1. Reason: Aoki et al. directly attribute secondary-siRNA-guided target RNA slicing to CSR-1. This supports both the specific siRNA-paired endoribonuclease term and its general RNA-endonuclease ancestor. The inactive-Argonaute reasoning applicable to human AGO4 or some WAGOs does not apply to this experimentally active slicer; both CSR-1 isoforms retain the same catalytic tetrad. The cached Aoki article is abstract-only, but explicitly identifies the target and reaction. Supporting Evidence: PMID:18007599 An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. PMID:34329465 both CSR-1 isoforms possess the same catalytic tetrad within the PIWI domain |
| GO:0090625 siRNA-mediated gene silencing by mRNA destabilization | IDA PMID:18007599 In vitro analyses of the production and activity of secondar... | ACCEPT | Summary: siRNA-mediated gene silencing by mRNA destabilization is supported for CSR-1. Reason: Direct CSR-1 secondary-siRNA-dependent target cleavage and translational-repression experiments support post-transcriptional silencing and, for the specific IDA row, cleavage-associated target destabilization. Positive licensing of other transcripts and the 2009 observation of unchanged abundance for tested chromosomal targets do not globally contradict this activity. Distinguish context and isoform; neither all CSR-1-bound RNAs nor every gene-regulatory role is silencing. Supporting Evidence: PMID:18007599 An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. PMID:18007599 Secondary rather than primary siRNAs may play a major role in the destabilization of target transcripts during RNAi in C. elegans. PMID:22231398 Nematode CSR-1 (Ago) promoted repression of FBF (PUF) target mRNAs in in vivo assays |
| GO:1903863 P granule assembly | IMP PMID:28182654 ELLI-1, a novel germline protein, modulates RNAi activity an... | KEEP AS NON CORE | Summary: P granule assembly is supported for CSR-1. Reason: The full 2017 paper directly includes csr-1 mutant alleles and abnormal enlarged P-granules despite its ELLI-1-focused title. Retain the curated assembly participation as control of proper granule accumulation/organization; the phenotype does not establish that CSR-1 is a structural nucleator or that loss completely prevents assembly. The paper explicitly leaves causal ordering between RNAi and granule defects unresolved. This organization phenotype is retained as a secondary role rather than a defining core molecular function. Supporting Evidence: PMID:28182654 eight of which contain mutations in known components of the CSR-1 complex (csr-1, ego-1, ekl-1, and drh-3). PMID:28182654 Loss of CSR-1 complex components results in a very specific, enlarged P-granule phenotype. |
| GO:0060967 negative regulation of gene silencing by regulatory ncRNA | IMP PMID:24360782 The C. elegans CSR-1 argonaute pathway counteracts epigeneti... | NEW | Summary: Retain the previously proposed CSR-1 gene-licensing function, independently supported by transcript recruitment experiments. Reason: CSR-1 performs regulatory work as a recruited small-RNA effector: tethering CSR-1 to a transcript protects it from piRNA-mediated silencing and can activate a silenced locus (PMID:24360783). This supplies both participation and direction for negative regulation of regulatory-ncRNA silencing. The older experiments are gene-level; later expression evidence points mainly to CSR-1b in the adult germline, so this is not asserted as an isoform-a-specific assay. The broader author-proposed positive regulation of gene expression row is omitted because GO:0060967 is its descendant. Supporting Evidence: PMID:24360783 the recruitment of CSR-1 to a transcript licenses expression of the transcript, protecting it from piRNA-mediated silencing. PMID:24360783 the recruitment of CSR-1 to a previously silenced locus transcriptionally activates its expression. PMID:24360782 We show that a transgene with RNAa activity also exhibits accumulation of cognate CSR-1 small RNAs. |
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Download this section (compressed HTML)Q: Do existing isoform-resolved CSR-1 IP libraries show mature miRNA enrichment above input and control IPs, after accounting for guide 5-prime chemistry and library biases? The focused report did not quantify this. A direct 22G-versus-miRNA loading/binding comparison would distinguish a retained physiological capacity from derived exclusion; no duplicate adjudication is requested.
Q: Which older gene-level chromatin, segregation, and licensing annotations should be explicitly remapped to CSR-1b Q27GU1 rather than represented on the CSR-1a accession H2KZD5?
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