CGH-1 (Conserved Germline Helicase 1) is a DEAD-box ATP-dependent RNA helicase and the C. elegans ortholog of yeast Dhh1p/human DDX6/Drosophila Me31B. It is germline-enriched, localizing to P granules (germ granules) and P-bodies (processing bodies), where it functions in post-transcriptional mRNA regulation. CGH-1 is essential for gametogenesis in both sexes and plays a protective role against physiological germline apoptosis - loss of cgh-1 was the first identified stimulus that triggers excessive germline apoptosis. CGH-1 forms RNA-dependent complexes with CAR-1, PAB-1, and OMA-1/2, functioning in translational repression and maternal mRNA protection during oogenesis. The protein also contributes to P-body assembly and is involved in stress granule dynamics.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0000932
P-body
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CGH-1 localization to P-bodies is well-supported by phylogenetic inference. The yeast ortholog Dhh1p is a core component of P-bodies, and direct experimental evidence in C. elegans confirms CGH-1 localizes to P-bodies (PMID:16207815, PMID:24367695).
Reason: IBA annotation is consistent with experimental IDA evidence in C. elegans showing CGH-1 localizes to P-bodies. P-body localization is a conserved feature of the DDX6/Dhh1p family across eukaryotes.
Supporting Evidence:
PMID:18692039
P-bodies contain complexes that inhibit translation and stimulate mRNA deadenylation, decapping, and decay
PMID:24367695
PAB-1 colocalizes with P-body components, CAR-1 and CGH-1
|
|
GO:0003729
mRNA binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CGH-1 is a DEAD-box RNA helicase that functions in mRNA metabolism. Its association with mRNA-containing complexes is well-established, and mRNA binding is a conserved function of DDX6 family helicases.
Reason: mRNA binding is expected for a DEAD-box helicase that functions in mRNA metabolism and localizes to mRNA-containing granules. The IBA inference from orthologs including yeast Dhh1 and plant homologs is phylogenetically sound.
Supporting Evidence:
PMID:16247027
CAR-1 is a component of an RNase-sensitive, multiprotein complex of conserved RNA-binding proteins
|
|
GO:0017148
negative regulation of translation
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Translational repression is a core function of CGH-1. Direct experimental evidence (IMP from PMID:18692039) supports this annotation in C. elegans. The IBA annotation is redundant with experimental evidence but correctly captures this conserved function.
Reason: IBA is consistent with direct experimental evidence from PMID:18692039 showing CGH-1 functions in negative regulation of translation in C. elegans. This is a conserved function of DDX6/Dhh1p family members.
Supporting Evidence:
PMID:18692039
P-bodies contain complexes that inhibit translation and stimulate mRNA deadenylation, decapping, and decay
|
|
GO:0010494
cytoplasmic stress granule
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CGH-1 localization to stress granules is supported by both IBA inference and direct experimental evidence (IDA from PMID:24844228). CGH-1 co-localizes with VBH-1 in stress-induced granules.
Reason: The IBA annotation is consistent with experimental IDA evidence showing CGH-1 localizes to cytoplasmic stress granules. This is a conserved feature of DDX6 family helicases.
Supporting Evidence:
PMID:24844228
VBH-1 colocalized with CGH-1 in the gonad core granules and large P granules observed during heat shock
|
|
GO:0033962
P-body assembly
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CGH-1 role in P-body assembly is supported by both IBA inference and direct experimental evidence (IMP from PMID:25061667). The yeast ortholog Dhh1p is essential for P-body assembly.
Reason: The IBA annotation is consistent with experimental IMP evidence showing CGH-1 is required for P-body assembly in C. elegans. This is a conserved function of the DDX6/Dhh1p family.
Supporting Evidence:
PMID:25061667
Accumulation of DCAP-1-containing granules under heat-shock is rapid, reversible and sensitive to cgh-1(RNAi)
|
|
GO:0034063
stress granule assembly
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CGH-1 involvement in stress granule assembly is inferred from phylogenetic analysis. While CGH-1 localizes to stress granules (PMID:24844228), direct evidence for its role in assembly is less clear in C. elegans than for P-bodies.
Reason: The IBA annotation from ortholog evidence is reasonable given CGH-1 localizes to stress granules and the DDX6 family is broadly involved in stress granule dynamics. CGH-1 co-localization with stress granule markers during heat shock supports this.
Supporting Evidence:
PMID:24844228
VBH-1 colocalized with CGH-1 in the gonad core granules and large P granules observed during heat shock
|
|
GO:0000166
nucleotide binding
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: CGH-1 contains a DEAD-box helicase domain with conserved Walker A motif for nucleotide binding. This is an accurate but very general annotation.
Reason: Correct but redundant with more specific ATP binding annotation. The protein contains conserved nucleotide binding motifs as expected for a DEAD-box helicase. The annotation is based on UniProtKB keyword mapping and is accurate.
|
|
GO:0003676
nucleic acid binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: CGH-1 is an RNA helicase with demonstrated RNA binding function. This term is accurate but overly general given the more specific mRNA binding annotation.
Reason: The InterPro domain-based annotation is correct - DEAD box helicases bind nucleic acids. This is redundant with but not contradicted by the more specific mRNA binding annotation.
|
|
GO:0003723
RNA binding
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: CGH-1 is an RNA helicase that binds RNA as part of its catalytic function and in forming ribonucleoprotein complexes with CAR-1, PAB-1, and other factors.
Reason: RNA binding is an essential activity for an RNA helicase. The UniProtKB keyword mapping correctly captures this core molecular function.
Supporting Evidence:
PMID:16247027
CAR-1 associates with the essential RNA helicase CGH-1
|
|
GO:0003724
RNA helicase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: CGH-1 is a DEAD-box RNA helicase with conserved catalytic domains. RNA helicase activity is directly supported by ISS annotation (PMID:11546739) based on sequence similarity to characterized helicases.
Reason: This is a core molecular function for CGH-1. The annotation is well-supported by domain architecture (DEAD box, helicase C-terminal domain) and sequence similarity to characterized RNA helicases.
Supporting Evidence:
PMID:11546739
cgh-1, a conserved predicted RNA helicase required for gametogenesis
|
|
GO:0004386
helicase activity
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: CGH-1 contains DEAD-box helicase domains. This is a correct but general annotation that is subsumed by the more specific RNA helicase activity annotation.
Reason: The UniProtKB keyword mapping is accurate. The term is general but not incorrect. RNA helicase activity is a more specific child term.
|
|
GO:0005524
ATP binding
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: CGH-1 contains a conserved Walker A motif (positions 87-94 per UniProt) for ATP binding. ATP binding is essential for DEAD-box helicase function.
Reason: ATP binding is a core molecular function for DEAD-box helicases and is structurally supported by the presence of the conserved ATP-binding helicase domain.
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: CGH-1 is cytoplasmic, localizing to cytoplasmic granules including P granules and P-bodies. This is confirmed by experimental evidence (PMID:11546739).
Reason: Cytoplasmic localization is accurate but general. More specific localizations (P granule, P-body, stress granule) are also annotated.
Supporting Evidence:
PMID:11546739
CGH-1 is expressed specifically in the germline and early embryo, and is localized to P granules and other possible mRNA-protein particles
|
|
GO:0006915
apoptotic process
|
IEA
GO_REF:0000043 |
MODIFY |
Summary: CGH-1 is involved in regulating apoptosis, specifically protecting against physiological germline apoptosis. However, this term is too general and the relationship is regulatory rather than being a core component of apoptosis.
Reason: The term is too general. CGH-1 does not execute apoptosis; rather it negatively regulates physiological germline apoptosis (PMID:11546739). The more specific annotation GO:0043066 (negative regulation of apoptotic process) is already present and more accurate.
Proposed replacements:
negative regulation of apoptotic process
Supporting Evidence:
PMID:11546739
It is also needed to prevent the physiological germline apoptosis mechanism killing essentially all developing oocytes, making lack of cgh-1 function the first stimulus identified that can trigger this mechanism
|
|
GO:0007283
spermatogenesis
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: CGH-1 is required for sperm function as demonstrated by experimental evidence (PMID:11546739). The UniProtKB keyword-based annotation is accurate.
Reason: The annotation is supported by experimental evidence from PMID:11546739 showing cgh-1 is required for sperm function. This is captured by the gamete generation IMP annotation but spermatogenesis specifically is accurate.
Supporting Evidence:
PMID:11546739
cgh-1 is required for oocyte and sperm function
|
|
GO:0016787
hydrolase activity
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: CGH-1 has ATP hydrolysis activity as part of its helicase function. This is a very general term but is accurate.
Reason: ATP hydrolysis is inherent to DEAD-box helicase function. This annotation is correct but general; the more specific ATP hydrolysis activity is also annotated.
|
|
GO:0016887
ATP hydrolysis activity
|
IEA
GO_REF:0000116 |
ACCEPT |
Summary: CGH-1 is a DEAD-box helicase that couples ATP hydrolysis to RNA unwinding. This is a core catalytic activity for the protein.
Reason: ATP hydrolysis activity is essential for DEAD-box helicase function. The Rhea-based annotation correctly captures this enzymatic activity.
|
|
GO:0017148
negative regulation of translation
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CGH-1 functions in translational repression, consistent with its localization to P-bodies and its role in mRNA regulation. This is also supported by experimental IMP evidence (PMID:18692039).
Reason: The ARBA machine learning annotation is consistent with experimental evidence showing CGH-1 negatively regulates translation. This is a core function of P-body components.
Supporting Evidence:
PMID:18692039
P-bodies contain complexes that inhibit translation and stimulate mRNA deadenylation, decapping, and decay
|
|
GO:0030154
cell differentiation
|
IEA
GO_REF:0000043 |
KEEP AS NON CORE |
Summary: CGH-1 is involved in germ cell development and gametogenesis, which involves cell differentiation. However, this term is very general.
Reason: While CGH-1 is involved in germ cell development, "cell differentiation" is very broad. The more specific annotations for gametogenesis, oogenesis, and spermatogenesis better capture CGH-1's role. This annotation is not incorrect but represents a secondary consequence of its primary functions.
|
|
GO:0033962
P-body assembly
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CGH-1 role in P-body assembly is well-supported by experimental IMP evidence (PMID:25061667) showing cgh-1(RNAi) reduces DCAP-1 granule formation.
Reason: The ARBA annotation is consistent with experimental evidence. P-body assembly is a conserved function of DDX6/Dhh1p family helicases.
Supporting Evidence:
PMID:25061667
Accumulation of DCAP-1-containing granules under heat-shock is rapid, reversible and sensitive to cgh-1(RNAi)
|
|
GO:0043186
P granule
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CGH-1 localization to P granules is very well-established by multiple IDA annotations (PMID:11546739, PMID:24367695). This is a core localization.
Reason: P granule localization is a key feature of CGH-1, supported by extensive experimental evidence including the original characterization paper.
Supporting Evidence:
PMID:11546739
CGH-1 is expressed specifically in the germline and early embryo, and is localized to P granules and other possible mRNA-protein particles
|
|
GO:0048477
oogenesis
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: CGH-1 is required for oocyte function as demonstrated experimentally (PMID:11546739). The UniProtKB keyword-based annotation is accurate.
Reason: The annotation is supported by experimental evidence showing cgh-1 is required for oocyte function and for protection from germline apoptosis during oogenesis.
Supporting Evidence:
PMID:11546739
cgh-1 is required for oocyte and sperm function
|
|
GO:0005515
protein binding
|
IPI
PMID:12445390 Integrating interactome, phenome, and transcriptome mapping ... |
MARK AS OVER ANNOTATED |
Summary: This annotation indicates CGH-1 binds to EDC-3 (Q21740) based on protein interaction data. However, "protein binding" is uninformative.
Reason: While CGH-1 does interact with other proteins, "protein binding" provides no information about the biological context or specificity of these interactions. The specific interactions with CAR-1, PAB-1, OMA-1 are more informative.
Supporting Evidence:
PMID:12445390
Integrating interactome, phenome, and transcriptome mapping data for the C.
|
|
GO:0005515
protein binding
|
IPI
PMID:14704431 A map of the interactome network of the metazoan C. elegans. |
MARK AS OVER ANNOTATED |
Summary: Large-scale protein interaction mapping study. "Protein binding" is uninformative as a molecular function annotation.
Reason: While the interaction data may be valid, "protein binding" as a GO term provides no functional insight. More specific annotations for the actual binding partners and biological context would be more useful.
Supporting Evidence:
PMID:14704431
Jan 2. A map of the interactome network of the metazoan C.
|
|
GO:0005515
protein binding
|
IPI
PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans... |
MARK AS OVER ANNOTATED |
Summary: Protein interaction study with EDC-3 as the binding partner. "Protein binding" is uninformative.
Reason: "Protein binding" provides no functional information. The specific interaction with EDC-3 (a decapping activator) is biologically meaningful in the context of P-body function, but this is not captured by the GO term.
Supporting Evidence:
PMID:19123269
Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network.
|
|
GO:0035770
ribonucleoprotein granule
|
IDA
PMID:25261697 Translational control of the oogenic program by components o... |
ACCEPT |
Summary: CGH-1 is part of OMA ribonucleoprotein particles, which are involved in translational control during oogenesis. This is direct experimental evidence.
Reason: The IDA annotation correctly captures CGH-1's localization to ribonucleoprotein granules. CGH-1 associates with OMA-1 in an RNA-dependent manner in oocyte RNPs.
Supporting Evidence:
PMID:25261697
OMA-1 is a component of oocyte RNPs
|
|
GO:0005515
protein binding
|
IPI
PMID:25261697 Translational control of the oogenic program by components o... |
MARK AS OVER ANNOTATED |
Summary: CGH-1 interacts with OMA-1 (G5EC86) as shown by co-purification studies. The interaction is RNA-dependent. "Protein binding" is uninformative.
Reason: The interaction with OMA-1 is biologically meaningful for understanding CGH-1's role in translational control during oogenesis, but "protein binding" does not capture this. The more informative annotation would describe the complex formation.
Supporting Evidence:
PMID:25261697
Sep 26. Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.
|
|
GO:0000932
P-body
|
IDA
PMID:24367695 PAB-1, a Caenorhabditis elegans poly(A)-binding protein, reg... |
ACCEPT |
Summary: Direct experimental evidence showing CGH-1 localizes to P-bodies. CGH-1 colocalizes with PAB-1 and CAR-1 in P-body structures.
Reason: Strong IDA evidence for P-body localization. This is consistent with CGH-1's role in mRNA metabolism and is a conserved feature of DDX6 family helicases.
Supporting Evidence:
PMID:24367695
PAB-1 colocalizes with P-body components, CAR-1 and CGH-1, in embryos and adult gonads
|
|
GO:0016071
mRNA metabolic process
|
IMP
PMID:24367695 PAB-1, a Caenorhabditis elegans poly(A)-binding protein, reg... |
ACCEPT |
Summary: CGH-1 mutants affect mRNA levels of germline genes. CGH-1 functions with PAB-1 and CAR-1 in regulating germline mRNA metabolism.
Reason: Experimental evidence demonstrates CGH-1's role in mRNA metabolism. The cgh-1 mutant shows altered mRNA levels for germline-enriched genes.
Supporting Evidence:
PMID:24367695
Although the mRNA level of msp-152 was increased in cgh-1 mutant, it was also significantly reduced by pab-1 RNAi
|
|
GO:0043186
P granule
|
IDA
PMID:24367695 PAB-1, a Caenorhabditis elegans poly(A)-binding protein, reg... |
ACCEPT |
Summary: Direct experimental evidence confirming CGH-1 localization to P granules. This is consistent with multiple other studies.
Reason: P granule localization is a core feature of CGH-1, demonstrated by multiple independent studies using immunofluorescence.
Supporting Evidence:
PMID:24367695
PAB-1 localizes to P granules and the cytoplasm in the germline
|
|
GO:0008340
determination of adult lifespan
|
IMP
PMID:25061667 Diverse functions of mRNA metabolism factors in stress defen... |
KEEP AS NON CORE |
Summary: cgh-1(RNAi) affects worm lifespan. P-body components including CGH-1 influence aging through their roles in mRNA metabolism and stress response.
Reason: While experimental evidence shows cgh-1 affects lifespan, this is likely a downstream consequence of its roles in mRNA metabolism and stress response rather than a direct/core function. Many genes affect lifespan indirectly.
Supporting Evidence:
PMID:25061667
PB components are important for normal lifespan and stress response
|
|
GO:0033962
P-body assembly
|
IMP
PMID:25061667 Diverse functions of mRNA metabolism factors in stress defen... |
ACCEPT |
Summary: cgh-1(RNAi) reduces accumulation of DCAP-1-containing P-body granules, demonstrating CGH-1 is required for P-body assembly.
Reason: Strong experimental evidence that CGH-1 is required for P-body assembly under stress conditions. This is a core function of DDX6/Dhh1p family helicases.
Supporting Evidence:
PMID:25061667
Accumulation of DCAP-1-containing granules under heat-shock is rapid, reversible and sensitive to cgh-1(RNAi)
|
|
GO:1990904
ribonucleoprotein complex
|
IDA
PMID:16247027 A complex containing the Sm protein CAR-1 and the RNA helica... |
ACCEPT |
Summary: CGH-1 is part of an RNA-dependent ribonucleoprotein complex with CAR-1. This complex is required for embryonic cytokinesis.
Reason: Direct experimental evidence showing CGH-1 co-purifies with CAR-1 in an RNA-dependent complex. The RNP complex function is central to CGH-1's biology.
Supporting Evidence:
PMID:16247027
CAR-1 is a component of an RNase-sensitive, multiprotein complex of conserved RNA-binding proteins
|
|
GO:0010494
cytoplasmic stress granule
|
IDA
PMID:24844228 The DEAD Box RNA helicase VBH-1 is a new player in the stres... |
ACCEPT |
Summary: CGH-1 localizes to stress-induced granules in gonads and embryos, co-localizing with VBH-1 during heat shock.
Reason: Direct experimental evidence showing CGH-1 localization to stress granules during heat shock. This is consistent with stress granule localization of DDX6 family members in other organisms.
Supporting Evidence:
PMID:24844228
VBH-1 colocalized with CGH-1 in the gonad core granules and large P granules observed during heat shock
|
|
GO:0043186
P granule
|
IDA
PMID:11546739 cgh-1, a conserved predicted RNA helicase required for gamet... |
ACCEPT |
Summary: The original characterization paper showing CGH-1 localizes to P granules. This is foundational evidence for CGH-1's subcellular localization.
Reason: Primary experimental evidence from the paper that first characterized CGH-1 function and localization. P granule localization is a core feature.
Supporting Evidence:
PMID:11546739
CGH-1 is expressed specifically in the germline and early embryo, and is localized to P granules and other possible mRNA-protein particles
|
|
GO:0017148
negative regulation of translation
|
IMP
PMID:18692039 Processing bodies and germ granules are distinct RNA granule... |
ACCEPT |
Summary: Experimental evidence demonstrating CGH-1 functions in translational repression. P-bodies containing CGH-1 inhibit translation of maternal mRNAs.
Reason: Direct experimental evidence for CGH-1's role in translational repression. This is a core function of the DDX6/Dhh1p family and consistent with P-body component function.
Supporting Evidence:
PMID:18692039
P-bodies contain complexes that inhibit translation and stimulate mRNA deadenylation, decapping, and decay
|
|
GO:0005515
protein binding
|
IPI
PMID:19269369 nhl-2 Modulates microRNA activity in Caenorhabditis elegans. |
MARK AS OVER ANNOTATED |
Summary: CGH-1 interacts with NHL-2, a microRNA pathway modulator. However, "protein binding" is uninformative.
Reason: The interaction with NHL-2 is potentially interesting for understanding CGH-1's role in post-transcriptional regulation, but "protein binding" as a GO term provides no functional insight.
Supporting Evidence:
PMID:19269369
nhl-2 Modulates microRNA activity in Caenorhabditis elegans.
|
|
GO:0000932
P-body
|
IDA
PMID:16207815 Caenorhabditis elegans decapping proteins localization and f... |
ACCEPT |
Summary: CGH-1 localization to P-bodies demonstrated in the context of decapping protein localization studies.
Reason: Direct experimental evidence for P-body localization. Consistent with multiple other studies and the conserved function of DDX6 family proteins.
Supporting Evidence:
PMID:16207815
Dcp2 is localized to P-granules
|
|
GO:0003724
RNA helicase activity
|
ISS
PMID:11546739 cgh-1, a conserved predicted RNA helicase required for gamet... |
ACCEPT |
Summary: RNA helicase activity inferred from sequence similarity to characterized DEAD-box RNA helicases. CGH-1 contains conserved DEAD box and helicase domains.
Reason: The ISS annotation is well-founded given the high conservation of DEAD-box helicase domains and the functional characterization of orthologs like Dhh1p. Crystal structures of CGH-1 domains (PDB:7DTJ, 7DTK) confirm the helicase fold.
Supporting Evidence:
PMID:11546739
cgh-1, a conserved predicted RNA helicase required for gametogenesis
|
|
GO:0007276
gamete generation
|
IMP
PMID:11546739 cgh-1, a conserved predicted RNA helicase required for gamet... |
ACCEPT |
Summary: cgh-1 mutants show defects in both oocyte and sperm function. CGH-1 is essential for gametogenesis in both sexes.
Reason: Primary experimental evidence demonstrating CGH-1 is required for gamete generation. This is a core biological function of the gene.
Supporting Evidence:
PMID:11546739
cgh-1 is required for oocyte and sperm function
|
|
GO:0016071
mRNA metabolic process
|
TAS
PMID:11546739 cgh-1, a conserved predicted RNA helicase required for gamet... |
ACCEPT |
Summary: CGH-1 functions in mRNA metabolism based on its localization to mRNA-containing granules and its homology to known mRNA metabolism factors.
Reason: The TAS annotation is supported by the paper's discussion of CGH-1's role in mRNA regulation during gametogenesis and its localization to P granules.
Supporting Evidence:
PMID:11546739
CGH-1 is expressed specifically in the germline and early embryo, and is localized to P granules and other possible mRNA-protein particles
|
|
GO:0043066
negative regulation of apoptotic process
|
IMP
PMID:11546739 cgh-1, a conserved predicted RNA helicase required for gamet... |
ACCEPT |
Summary: Loss of cgh-1 causes excessive germline apoptosis, demonstrating CGH-1 normally protects developing oocytes from physiological germline apoptosis. This was the first identified trigger of excessive germline apoptosis.
Reason: This is a defining feature of CGH-1 function discovered in the original characterization paper. CGH-1 is required to prevent the germline apoptosis mechanism from killing essentially all developing oocytes.
Supporting Evidence:
PMID:11546739
It is also needed to prevent the physiological germline apoptosis mechanism killing essentially all developing oocytes, making lack of cgh-1 function the first stimulus identified that can trigger this mechanism
|
Q: What are the specific mRNA targets of CGH-1-mediated translational repression?
Q: How does CGH-1 coordinate with the apoptosis pathway to protect developing oocytes?
Q: What is the structural basis for CGH-1's interaction with CAR-1?
Q: Does CGH-1 function differently in P granules vs P-bodies?
Experiment: CLIP-seq or related methods to identify direct mRNA targets of CGH-1
Hypothesis: CGH-1 binds specific maternal mRNAs to protect them from degradation and regulate their translation
Experiment: Structure-function analysis of CGH-1 helicase activity vs RNA binding in apoptosis protection
Hypothesis: CGH-1's anti-apoptotic function may require RNA binding but not necessarily helicase activity
Experiment: Live imaging of CGH-1 dynamics between P granules and P-bodies during oocyte development
Hypothesis: CGH-1 shuttles between P granules and P-bodies to coordinate mRNA fate during oogenesis
id: Q95YF3
gene_symbol: cgh-1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:6239
label: Caenorhabditis elegans
description: CGH-1 (Conserved Germline Helicase 1) is a DEAD-box ATP-dependent
RNA helicase and the C. elegans ortholog of yeast Dhh1p/human DDX6/Drosophila
Me31B. It is germline-enriched, localizing to P granules (germ granules) and
P-bodies (processing bodies), where it functions in post-transcriptional mRNA
regulation. CGH-1 is essential for gametogenesis in both sexes and plays a
protective role against physiological germline apoptosis - loss of cgh-1 was
the first identified stimulus that triggers excessive germline apoptosis.
CGH-1 forms RNA-dependent complexes with CAR-1, PAB-1, and OMA-1/2,
functioning in translational repression and maternal mRNA protection during
oogenesis. The protein also contributes to P-body assembly and is involved in
stress granule dynamics.
existing_annotations:
- term:
id: GO:0000932
label: P-body
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: CGH-1 localization to P-bodies is well-supported by phylogenetic
inference. The yeast ortholog Dhh1p is a core component of P-bodies, and
direct experimental evidence in C. elegans confirms CGH-1 localizes to
P-bodies (PMID:16207815, PMID:24367695).
action: ACCEPT
reason: IBA annotation is consistent with experimental IDA evidence in C.
elegans showing CGH-1 localizes to P-bodies. P-body localization is a
conserved feature of the DDX6/Dhh1p family across eukaryotes.
supported_by:
- reference_id: PMID:18692039
supporting_text: P-bodies contain complexes that inhibit translation and
stimulate mRNA deadenylation, decapping, and decay
- reference_id: PMID:24367695
supporting_text: PAB-1 colocalizes with P-body components, CAR-1 and CGH-1
- term:
id: GO:0003729
label: mRNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: CGH-1 is a DEAD-box RNA helicase that functions in mRNA metabolism.
Its association with mRNA-containing complexes is well-established, and
mRNA binding is a conserved function of DDX6 family helicases.
action: ACCEPT
reason: mRNA binding is expected for a DEAD-box helicase that functions in
mRNA metabolism and localizes to mRNA-containing granules. The IBA
inference from orthologs including yeast Dhh1 and plant homologs is
phylogenetically sound.
supported_by:
- reference_id: PMID:16247027
supporting_text: CAR-1 is a component of an RNase-sensitive, multiprotein
complex of conserved RNA-binding proteins
- term:
id: GO:0017148
label: negative regulation of translation
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Translational repression is a core function of CGH-1. Direct
experimental evidence (IMP from PMID:18692039) supports this annotation in
C. elegans. The IBA annotation is redundant with experimental evidence but
correctly captures this conserved function.
action: ACCEPT
reason: IBA is consistent with direct experimental evidence from
PMID:18692039 showing CGH-1 functions in negative regulation of
translation in C. elegans. This is a conserved function of DDX6/Dhh1p
family members.
supported_by:
- reference_id: PMID:18692039
supporting_text: P-bodies contain complexes that inhibit translation and
stimulate mRNA deadenylation, decapping, and decay
- term:
id: GO:0010494
label: cytoplasmic stress granule
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: CGH-1 localization to stress granules is supported by both IBA
inference and direct experimental evidence (IDA from PMID:24844228). CGH-1
co-localizes with VBH-1 in stress-induced granules.
action: ACCEPT
reason: The IBA annotation is consistent with experimental IDA evidence
showing CGH-1 localizes to cytoplasmic stress granules. This is a
conserved feature of DDX6 family helicases.
supported_by:
- reference_id: PMID:24844228
supporting_text: VBH-1 colocalized with CGH-1 in the gonad core granules
and large P granules observed during heat shock
- term:
id: GO:0033962
label: P-body assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: CGH-1 role in P-body assembly is supported by both IBA inference
and direct experimental evidence (IMP from PMID:25061667). The yeast
ortholog Dhh1p is essential for P-body assembly.
action: ACCEPT
reason: The IBA annotation is consistent with experimental IMP evidence
showing CGH-1 is required for P-body assembly in C. elegans. This is a
conserved function of the DDX6/Dhh1p family.
supported_by:
- reference_id: PMID:25061667
supporting_text: Accumulation of DCAP-1-containing granules under
heat-shock is rapid, reversible and sensitive to cgh-1(RNAi)
- term:
id: GO:0034063
label: stress granule assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: CGH-1 involvement in stress granule assembly is inferred from
phylogenetic analysis. While CGH-1 localizes to stress granules
(PMID:24844228), direct evidence for its role in assembly is less clear in
C. elegans than for P-bodies.
action: ACCEPT
reason: The IBA annotation from ortholog evidence is reasonable given CGH-1
localizes to stress granules and the DDX6 family is broadly involved in
stress granule dynamics. CGH-1 co-localization with stress granule markers
during heat shock supports this.
supported_by:
- reference_id: PMID:24844228
supporting_text: VBH-1 colocalized with CGH-1 in the gonad core granules
and large P granules observed during heat shock
- term:
id: GO:0000166
label: nucleotide binding
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 contains a DEAD-box helicase domain with conserved Walker A
motif for nucleotide binding. This is an accurate but very general
annotation.
action: ACCEPT
reason: Correct but redundant with more specific ATP binding annotation. The
protein contains conserved nucleotide binding motifs as expected for a
DEAD-box helicase. The annotation is based on UniProtKB keyword mapping
and is accurate.
- term:
id: GO:0003676
label: nucleic acid binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: CGH-1 is an RNA helicase with demonstrated RNA binding function.
This term is accurate but overly general given the more specific mRNA
binding annotation.
action: ACCEPT
reason: The InterPro domain-based annotation is correct - DEAD box helicases
bind nucleic acids. This is redundant with but not contradicted by the
more specific mRNA binding annotation.
- term:
id: GO:0003723
label: RNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 is an RNA helicase that binds RNA as part of its catalytic
function and in forming ribonucleoprotein complexes with CAR-1, PAB-1, and
other factors.
action: ACCEPT
reason: RNA binding is an essential activity for an RNA helicase. The
UniProtKB keyword mapping correctly captures this core molecular function.
supported_by:
- reference_id: PMID:16247027
supporting_text: CAR-1 associates with the essential RNA helicase CGH-1
- term:
id: GO:0003724
label: RNA helicase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: CGH-1 is a DEAD-box RNA helicase with conserved catalytic domains.
RNA helicase activity is directly supported by ISS annotation
(PMID:11546739) based on sequence similarity to characterized helicases.
action: ACCEPT
reason: This is a core molecular function for CGH-1. The annotation is
well-supported by domain architecture (DEAD box, helicase C-terminal
domain) and sequence similarity to characterized RNA helicases.
supported_by:
- reference_id: PMID:11546739
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis
- term:
id: GO:0004386
label: helicase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 contains DEAD-box helicase domains. This is a correct but
general annotation that is subsumed by the more specific RNA helicase
activity annotation.
action: ACCEPT
reason: The UniProtKB keyword mapping is accurate. The term is general but
not incorrect. RNA helicase activity is a more specific child term.
- term:
id: GO:0005524
label: ATP binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: CGH-1 contains a conserved Walker A motif (positions 87-94 per
UniProt) for ATP binding. ATP binding is essential for DEAD-box helicase
function.
action: ACCEPT
reason: ATP binding is a core molecular function for DEAD-box helicases and
is structurally supported by the presence of the conserved ATP-binding
helicase domain.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: CGH-1 is cytoplasmic, localizing to cytoplasmic granules including
P granules and P-bodies. This is confirmed by experimental evidence
(PMID:11546739).
action: ACCEPT
reason: Cytoplasmic localization is accurate but general. More specific
localizations (P granule, P-body, stress granule) are also annotated.
supported_by:
- reference_id: PMID:11546739
supporting_text: CGH-1 is expressed specifically in the germline and early
embryo, and is localized to P granules and other possible mRNA-protein
particles
- term:
id: GO:0006915
label: apoptotic process
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 is involved in regulating apoptosis, specifically protecting
against physiological germline apoptosis. However, this term is too
general and the relationship is regulatory rather than being a core
component of apoptosis.
action: MODIFY
reason: The term is too general. CGH-1 does not execute apoptosis; rather it
negatively regulates physiological germline apoptosis (PMID:11546739). The
more specific annotation GO:0043066 (negative regulation of apoptotic
process) is already present and more accurate.
proposed_replacement_terms:
- id: GO:0043066
label: negative regulation of apoptotic process
supported_by:
- reference_id: PMID:11546739
supporting_text: It is also needed to prevent the physiological germline
apoptosis mechanism killing essentially all developing oocytes, making
lack of cgh-1 function the first stimulus identified that can trigger
this mechanism
- term:
id: GO:0007283
label: spermatogenesis
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 is required for sperm function as demonstrated by
experimental evidence (PMID:11546739). The UniProtKB keyword-based
annotation is accurate.
action: ACCEPT
reason: The annotation is supported by experimental evidence from
PMID:11546739 showing cgh-1 is required for sperm function. This is
captured by the gamete generation IMP annotation but spermatogenesis
specifically is accurate.
supported_by:
- reference_id: PMID:11546739
supporting_text: cgh-1 is required for oocyte and sperm function
- term:
id: GO:0016787
label: hydrolase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 has ATP hydrolysis activity as part of its helicase function.
This is a very general term but is accurate.
action: ACCEPT
reason: ATP hydrolysis is inherent to DEAD-box helicase function. This
annotation is correct but general; the more specific ATP hydrolysis
activity is also annotated.
- term:
id: GO:0016887
label: ATP hydrolysis activity
evidence_type: IEA
original_reference_id: GO_REF:0000116
review:
summary: CGH-1 is a DEAD-box helicase that couples ATP hydrolysis to RNA
unwinding. This is a core catalytic activity for the protein.
action: ACCEPT
reason: ATP hydrolysis activity is essential for DEAD-box helicase function.
The Rhea-based annotation correctly captures this enzymatic activity.
- term:
id: GO:0017148
label: negative regulation of translation
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: CGH-1 functions in translational repression, consistent with its
localization to P-bodies and its role in mRNA regulation. This is also
supported by experimental IMP evidence (PMID:18692039).
action: ACCEPT
reason: The ARBA machine learning annotation is consistent with experimental
evidence showing CGH-1 negatively regulates translation. This is a core
function of P-body components.
supported_by:
- reference_id: PMID:18692039
supporting_text: P-bodies contain complexes that inhibit translation and
stimulate mRNA deadenylation, decapping, and decay
- term:
id: GO:0030154
label: cell differentiation
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 is involved in germ cell development and gametogenesis, which
involves cell differentiation. However, this term is very general.
action: KEEP_AS_NON_CORE
reason: While CGH-1 is involved in germ cell development, "cell
differentiation" is very broad. The more specific annotations for
gametogenesis, oogenesis, and spermatogenesis better capture CGH-1's role.
This annotation is not incorrect but represents a secondary consequence of
its primary functions.
- term:
id: GO:0033962
label: P-body assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: CGH-1 role in P-body assembly is well-supported by experimental IMP
evidence (PMID:25061667) showing cgh-1(RNAi) reduces DCAP-1 granule
formation.
action: ACCEPT
reason: The ARBA annotation is consistent with experimental evidence. P-body
assembly is a conserved function of DDX6/Dhh1p family helicases.
supported_by:
- reference_id: PMID:25061667
supporting_text: Accumulation of DCAP-1-containing granules under
heat-shock is rapid, reversible and sensitive to cgh-1(RNAi)
- term:
id: GO:0043186
label: P granule
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: CGH-1 localization to P granules is very well-established by
multiple IDA annotations (PMID:11546739, PMID:24367695). This is a core
localization.
action: ACCEPT
reason: P granule localization is a key feature of CGH-1, supported by
extensive experimental evidence including the original characterization
paper.
supported_by:
- reference_id: PMID:11546739
supporting_text: CGH-1 is expressed specifically in the germline and early
embryo, and is localized to P granules and other possible mRNA-protein
particles
- term:
id: GO:0048477
label: oogenesis
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: CGH-1 is required for oocyte function as demonstrated
experimentally (PMID:11546739). The UniProtKB keyword-based annotation is
accurate.
action: ACCEPT
reason: The annotation is supported by experimental evidence showing cgh-1
is required for oocyte function and for protection from germline apoptosis
during oogenesis.
supported_by:
- reference_id: PMID:11546739
supporting_text: cgh-1 is required for oocyte and sperm function
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12445390
review:
summary: This annotation indicates CGH-1 binds to EDC-3 (Q21740) based on
protein interaction data. However, "protein binding" is uninformative.
action: MARK_AS_OVER_ANNOTATED
reason: While CGH-1 does interact with other proteins, "protein binding"
provides no information about the biological context or specificity of
these interactions. The specific interactions with CAR-1, PAB-1, OMA-1 are
more informative.
supported_by:
- reference_id: PMID:12445390
supporting_text: Integrating interactome, phenome, and transcriptome
mapping data for the C.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:14704431
review:
summary: Large-scale protein interaction mapping study. "Protein binding" is
uninformative as a molecular function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: While the interaction data may be valid, "protein binding" as a GO
term provides no functional insight. More specific annotations for the
actual binding partners and biological context would be more useful.
supported_by:
- reference_id: PMID:14704431
supporting_text: Jan 2. A map of the interactome network of the metazoan
C.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19123269
review:
summary: Protein interaction study with EDC-3 as the binding partner.
"Protein binding" is uninformative.
action: MARK_AS_OVER_ANNOTATED
reason: '"Protein binding" provides no functional information. The specific interaction
with EDC-3 (a decapping activator) is biologically meaningful in the context
of P-body function, but this is not captured by the GO term.'
supported_by:
- reference_id: PMID:19123269
supporting_text: Empirically controlled mapping of the Caenorhabditis
elegans protein-protein interactome network.
- term:
id: GO:0035770
label: ribonucleoprotein granule
evidence_type: IDA
original_reference_id: PMID:25261697
review:
summary: CGH-1 is part of OMA ribonucleoprotein particles, which are
involved in translational control during oogenesis. This is direct
experimental evidence.
action: ACCEPT
reason: The IDA annotation correctly captures CGH-1's localization to
ribonucleoprotein granules. CGH-1 associates with OMA-1 in an
RNA-dependent manner in oocyte RNPs.
supported_by:
- reference_id: PMID:25261697
supporting_text: OMA-1 is a component of oocyte RNPs
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25261697
review:
summary: CGH-1 interacts with OMA-1 (G5EC86) as shown by co-purification
studies. The interaction is RNA-dependent. "Protein binding" is
uninformative.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction with OMA-1 is biologically meaningful for
understanding CGH-1's role in translational control during oogenesis, but
"protein binding" does not capture this. The more informative annotation
would describe the complex formation.
supported_by:
- reference_id: PMID:25261697
supporting_text: Sep 26. Translational control of the oogenic program by
components of OMA ribonucleoprotein particles in Caenorhabditis elegans.
- term:
id: GO:0000932
label: P-body
evidence_type: IDA
original_reference_id: PMID:24367695
review:
summary: Direct experimental evidence showing CGH-1 localizes to P-bodies.
CGH-1 colocalizes with PAB-1 and CAR-1 in P-body structures.
action: ACCEPT
reason: Strong IDA evidence for P-body localization. This is consistent with
CGH-1's role in mRNA metabolism and is a conserved feature of DDX6 family
helicases.
supported_by:
- reference_id: PMID:24367695
supporting_text: PAB-1 colocalizes with P-body components, CAR-1 and
CGH-1, in embryos and adult gonads
- term:
id: GO:0016071
label: mRNA metabolic process
evidence_type: IMP
original_reference_id: PMID:24367695
review:
summary: CGH-1 mutants affect mRNA levels of germline genes. CGH-1 functions
with PAB-1 and CAR-1 in regulating germline mRNA metabolism.
action: ACCEPT
reason: Experimental evidence demonstrates CGH-1's role in mRNA metabolism.
The cgh-1 mutant shows altered mRNA levels for germline-enriched genes.
supported_by:
- reference_id: PMID:24367695
supporting_text: Although the mRNA level of msp-152 was increased in cgh-1
mutant, it was also significantly reduced by pab-1 RNAi
- term:
id: GO:0043186
label: P granule
evidence_type: IDA
original_reference_id: PMID:24367695
review:
summary: Direct experimental evidence confirming CGH-1 localization to P
granules. This is consistent with multiple other studies.
action: ACCEPT
reason: P granule localization is a core feature of CGH-1, demonstrated by
multiple independent studies using immunofluorescence.
supported_by:
- reference_id: PMID:24367695
supporting_text: PAB-1 localizes to P granules and the cytoplasm in the
germline
- term:
id: GO:0008340
label: determination of adult lifespan
evidence_type: IMP
original_reference_id: PMID:25061667
review:
summary: cgh-1(RNAi) affects worm lifespan. P-body components including
CGH-1 influence aging through their roles in mRNA metabolism and stress
response.
action: KEEP_AS_NON_CORE
reason: While experimental evidence shows cgh-1 affects lifespan, this is
likely a downstream consequence of its roles in mRNA metabolism and stress
response rather than a direct/core function. Many genes affect lifespan
indirectly.
supported_by:
- reference_id: PMID:25061667
supporting_text: PB components are important for normal lifespan and
stress response
- term:
id: GO:0033962
label: P-body assembly
evidence_type: IMP
original_reference_id: PMID:25061667
review:
summary: cgh-1(RNAi) reduces accumulation of DCAP-1-containing P-body
granules, demonstrating CGH-1 is required for P-body assembly.
action: ACCEPT
reason: Strong experimental evidence that CGH-1 is required for P-body
assembly under stress conditions. This is a core function of DDX6/Dhh1p
family helicases.
supported_by:
- reference_id: PMID:25061667
supporting_text: Accumulation of DCAP-1-containing granules under
heat-shock is rapid, reversible and sensitive to cgh-1(RNAi)
- term:
id: GO:1990904
label: ribonucleoprotein complex
evidence_type: IDA
original_reference_id: PMID:16247027
review:
summary: CGH-1 is part of an RNA-dependent ribonucleoprotein complex with
CAR-1. This complex is required for embryonic cytokinesis.
action: ACCEPT
reason: Direct experimental evidence showing CGH-1 co-purifies with CAR-1 in
an RNA-dependent complex. The RNP complex function is central to CGH-1's
biology.
supported_by:
- reference_id: PMID:16247027
supporting_text: CAR-1 is a component of an RNase-sensitive, multiprotein
complex of conserved RNA-binding proteins
- term:
id: GO:0010494
label: cytoplasmic stress granule
evidence_type: IDA
original_reference_id: PMID:24844228
review:
summary: CGH-1 localizes to stress-induced granules in gonads and embryos,
co-localizing with VBH-1 during heat shock.
action: ACCEPT
reason: Direct experimental evidence showing CGH-1 localization to stress
granules during heat shock. This is consistent with stress granule
localization of DDX6 family members in other organisms.
supported_by:
- reference_id: PMID:24844228
supporting_text: VBH-1 colocalized with CGH-1 in the gonad core granules
and large P granules observed during heat shock
- term:
id: GO:0043186
label: P granule
evidence_type: IDA
original_reference_id: PMID:11546739
review:
summary: The original characterization paper showing CGH-1 localizes to P
granules. This is foundational evidence for CGH-1's subcellular
localization.
action: ACCEPT
reason: Primary experimental evidence from the paper that first
characterized CGH-1 function and localization. P granule localization is a
core feature.
supported_by:
- reference_id: PMID:11546739
supporting_text: CGH-1 is expressed specifically in the germline and early
embryo, and is localized to P granules and other possible mRNA-protein
particles
- term:
id: GO:0017148
label: negative regulation of translation
evidence_type: IMP
original_reference_id: PMID:18692039
review:
summary: Experimental evidence demonstrating CGH-1 functions in
translational repression. P-bodies containing CGH-1 inhibit translation of
maternal mRNAs.
action: ACCEPT
reason: Direct experimental evidence for CGH-1's role in translational
repression. This is a core function of the DDX6/Dhh1p family and
consistent with P-body component function.
supported_by:
- reference_id: PMID:18692039
supporting_text: P-bodies contain complexes that inhibit translation and
stimulate mRNA deadenylation, decapping, and decay
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19269369
review:
summary: CGH-1 interacts with NHL-2, a microRNA pathway modulator. However,
"protein binding" is uninformative.
action: MARK_AS_OVER_ANNOTATED
reason: The interaction with NHL-2 is potentially interesting for
understanding CGH-1's role in post-transcriptional regulation, but
"protein binding" as a GO term provides no functional insight.
supported_by:
- reference_id: PMID:19269369
supporting_text: nhl-2 Modulates microRNA activity in Caenorhabditis
elegans.
- term:
id: GO:0000932
label: P-body
evidence_type: IDA
original_reference_id: PMID:16207815
review:
summary: CGH-1 localization to P-bodies demonstrated in the context of
decapping protein localization studies.
action: ACCEPT
reason: Direct experimental evidence for P-body localization. Consistent
with multiple other studies and the conserved function of DDX6 family
proteins.
supported_by:
- reference_id: PMID:16207815
supporting_text: Dcp2 is localized to P-granules
- term:
id: GO:0003724
label: RNA helicase activity
evidence_type: ISS
original_reference_id: PMID:11546739
review:
summary: RNA helicase activity inferred from sequence similarity to
characterized DEAD-box RNA helicases. CGH-1 contains conserved DEAD box
and helicase domains.
action: ACCEPT
reason: The ISS annotation is well-founded given the high conservation of
DEAD-box helicase domains and the functional characterization of orthologs
like Dhh1p. Crystal structures of CGH-1 domains (PDB:7DTJ, 7DTK) confirm
the helicase fold.
supported_by:
- reference_id: PMID:11546739
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis
- term:
id: GO:0007276
label: gamete generation
evidence_type: IMP
original_reference_id: PMID:11546739
review:
summary: cgh-1 mutants show defects in both oocyte and sperm function. CGH-1
is essential for gametogenesis in both sexes.
action: ACCEPT
reason: Primary experimental evidence demonstrating CGH-1 is required for
gamete generation. This is a core biological function of the gene.
supported_by:
- reference_id: PMID:11546739
supporting_text: cgh-1 is required for oocyte and sperm function
- term:
id: GO:0016071
label: mRNA metabolic process
evidence_type: TAS
original_reference_id: PMID:11546739
review:
summary: CGH-1 functions in mRNA metabolism based on its localization to
mRNA-containing granules and its homology to known mRNA metabolism
factors.
action: ACCEPT
reason: The TAS annotation is supported by the paper's discussion of CGH-1's
role in mRNA regulation during gametogenesis and its localization to P
granules.
supported_by:
- reference_id: PMID:11546739
supporting_text: CGH-1 is expressed specifically in the germline and early
embryo, and is localized to P granules and other possible mRNA-protein
particles
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: IMP
original_reference_id: PMID:11546739
review:
summary: Loss of cgh-1 causes excessive germline apoptosis, demonstrating
CGH-1 normally protects developing oocytes from physiological germline
apoptosis. This was the first identified trigger of excessive germline
apoptosis.
action: ACCEPT
reason: This is a defining feature of CGH-1 function discovered in the
original characterization paper. CGH-1 is required to prevent the germline
apoptosis mechanism from killing essentially all developing oocytes.
supported_by:
- reference_id: PMID:11546739
supporting_text: It is also needed to prevent the physiological germline
apoptosis mechanism killing essentially all developing oocytes, making
lack of cgh-1 function the first stimulus identified that can trigger
this mechanism
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with
GO terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings:
- statement: CGH-1 is part of a well-conserved family of DEAD-box RNA
helicases (DDX6/Dhh1p subfamily) with conserved functions in P-body
formation, mRNA regulation, and translational repression across
eukaryotes.
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
Location vocabulary mapping
findings: []
- id: GO_REF:0000116
title: Automatic Gene Ontology annotation based on Rhea mapping
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning
models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:11546739
title: cgh-1, a conserved predicted RNA helicase required for gametogenesis
and protection from physiological germline apoptosis in C. elegans.
findings:
- statement: CGH-1 is the C. elegans ortholog of yeast Dhh1p/Ste13, human
DDX6/RCK/p54, and Drosophila Me31B
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis and protection from physiological germline apoptosis in C.
elegans.
- statement: CGH-1 is expressed specifically in the germline and early embryo
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis and protection from physiological germline apoptosis in C.
elegans.
- statement: CGH-1 localizes to P granules
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis and protection from physiological germline apoptosis in C.
elegans.
- statement: cgh-1 is required for both oocyte and sperm function
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis and protection from physiological germline apoptosis in C.
elegans.
- statement: Loss of cgh-1 triggers excessive germline apoptosis - the first
identified stimulus for this mechanism
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis and protection from physiological germline apoptosis in C.
elegans.
- statement: CGH-1 protects developing oocytes from physiological germline
apoptosis
supporting_text: cgh-1, a conserved predicted RNA helicase required for
gametogenesis and protection from physiological germline apoptosis in C.
elegans.
- id: PMID:12445390
title: Integrating interactome, phenome, and transcriptome mapping data for
the C. elegans germline.
findings:
- statement: Large-scale interaction study identifying CGH-1 binding partners
supporting_text: Integrating interactome, phenome, and transcriptome mapping
data for the C. elegans germline.
- id: PMID:14704431
title: A map of the interactome network of the metazoan C. elegans.
findings:
- statement: Systematic protein interaction mapping including CGH-1
supporting_text: A map of the interactome network of the metazoan C.
elegans.
- id: PMID:16207815
title: Caenorhabditis elegans decapping proteins localization and functional
analysis of Dcp1, Dcp2, and DcpS during embryogenesis.
findings:
- statement: CGH-1 localizes to P-bodies with decapping proteins
supporting_text: 'Caenorhabditis elegans decapping proteins: localization and
functional analysis of Dcp1, Dcp2, and DcpS during embryogenesis.'
- id: PMID:16247027
title: A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is
required for embryonic cytokinesis in Caenorhabditis elegans.
findings:
- statement: CGH-1 co-purifies with CAR-1 in an RNA-dependent
ribonucleoprotein complex
supporting_text: A complex containing the Sm protein CAR-1 and the RNA
helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis
elegans.
- statement: CGH-1 controls the localization of CAR-1
supporting_text: A complex containing the Sm protein CAR-1 and the RNA
helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis
elegans.
- statement: CGH-1 and CAR-1 together regulate anaphase spindle structure
during embryonic cytokinesis
supporting_text: A complex containing the Sm protein CAR-1 and the RNA
helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis
elegans.
- statement: Partial depletion of CGH-1 phenocopies CAR-1 inhibition
supporting_text: A complex containing the Sm protein CAR-1 and the RNA
helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis
elegans.
- statement: The CGH-1/CAR-1 complex is RNase-sensitive
supporting_text: A complex containing the Sm protein CAR-1 and the RNA
helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis
elegans.
- id: PMID:18692039
title: Processing bodies and germ granules are distinct RNA granules that
interact in C. elegans embryos.
findings:
- statement: P-bodies and germ granules (P granules) are distinct but
interacting RNA granules
supporting_text: Processing bodies and germ granules are distinct RNA
granules that interact in C. elegans embryos.
- statement: P-bodies contain complexes that inhibit translation
supporting_text: Processing bodies and germ granules are distinct RNA
granules that interact in C. elegans embryos.
- statement: CGH-1 is found in both P-bodies and P granules
supporting_text: Processing bodies and germ granules are distinct RNA
granules that interact in C. elegans embryos.
- statement: P-bodies mature differently in somatic vs germline blastomeres
supporting_text: Processing bodies and germ granules are distinct RNA
granules that interact in C. elegans embryos.
- id: PMID:19123269
title: Empirically controlled mapping of the Caenorhabditis elegans
protein-protein interactome network.
findings:
- statement: High-confidence protein interaction data for CGH-1
supporting_text: Empirically controlled mapping of the Caenorhabditis
elegans protein-protein interactome network.
- id: PMID:19269369
title: nhl-2 Modulates microRNA activity in Caenorhabditis elegans.
findings:
- statement: CGH-1 interacts with NHL-2, a microRNA pathway component
supporting_text: nhl-2 Modulates microRNA activity in Caenorhabditis
elegans.
- id: PMID:24367695
title: PAB-1, a Caenorhabditis elegans poly(A)-binding protein, regulates mRNA
metabolism in germline by interacting with CGH-1 and CAR-1.
findings:
- statement: PAB-1 colocalizes with CGH-1 and CAR-1 at P-body granules
supporting_text: PAB-1, a Caenorhabditis elegans poly(A)-binding protein,
regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1.
- statement: PAB-1 is a component of P-bodies that interacts with CGH-1 and
CAR-1
supporting_text: PAB-1, a Caenorhabditis elegans poly(A)-binding protein,
regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1.
- statement: CGH-1 and PAB-1 mutually affect each others localization
supporting_text: PAB-1, a Caenorhabditis elegans poly(A)-binding protein,
regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1.
- statement: The mRNA level of msp-152 is increased in cgh-1 mutant
supporting_text: PAB-1, a Caenorhabditis elegans poly(A)-binding protein,
regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1.
- statement: PAB-1 positively regulates mRNA levels in coordination with CGH-1
and CAR-1
supporting_text: PAB-1, a Caenorhabditis elegans poly(A)-binding protein,
regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1.
- id: PMID:24844228
title: The DEAD Box RNA helicase VBH-1 is a new player in the stress response
in C. elegans.
findings:
- statement: VBH-1 colocalizes with CGH-1 in large foci during heat shock
supporting_text: The DEAD Box RNA helicase VBH-1 is a new player in the
stress response in C. elegans.
- statement: CGH-1 localizes to stress granule-like structures during stress
supporting_text: The DEAD Box RNA helicase VBH-1 is a new player in the
stress response in C. elegans.
- statement: VBH-1 and CGH-1 associate with some of the same RNPs during heat
shock
supporting_text: The DEAD Box RNA helicase VBH-1 is a new player in the
stress response in C. elegans.
- id: PMID:25061667
title: Diverse functions of mRNA metabolism factors in stress defense and
aging of Caenorhabditis elegans.
findings:
- statement: P-body formation requires CGH-1 (cgh-1 RNAi prevents DCAP-1
granule accumulation)
supporting_text: Diverse functions of mRNA metabolism factors in stress
defense and aging of Caenorhabditis elegans.
- statement: P-body components including CGH-1 are important for normal
lifespan
supporting_text: Diverse functions of mRNA metabolism factors in stress
defense and aging of Caenorhabditis elegans.
- statement: cgh-1 RNAi affects stress granule dynamics
supporting_text: Diverse functions of mRNA metabolism factors in stress
defense and aging of Caenorhabditis elegans.
- id: PMID:25261697
title: Translational control of the oogenic program by components of OMA
ribonucleoprotein particles in Caenorhabditis elegans.
findings:
- statement: CGH-1 is an OMA-1-associated protein in oocyte RNPs
supporting_text: Translational control of the oogenic program by components
of OMA ribonucleoprotein particles in Caenorhabditis elegans.
- statement: CGH-1 interacts with OMA-1 in an RNA-dependent manner
supporting_text: Translational control of the oogenic program by components
of OMA ribonucleoprotein particles in Caenorhabditis elegans.
- statement: OMA RNPs function in translational repression of target mRNAs
supporting_text: Translational control of the oogenic program by components
of OMA ribonucleoprotein particles in Caenorhabditis elegans.
core_functions:
- molecular_function:
id: GO:0003724
label: RNA helicase activity
description: CGH-1 is a DEAD-box RNA helicase with conserved ATP-binding and
helicase domains. Crystal structures (PDB:7DTJ, 7DTK) confirm the helicase
fold. RNA helicase activity is inferred from sequence similarity to
characterized orthologs (ISS).
locations:
- id: GO:0043186
label: P granule
- id: GO:0000932
label: P-body
directly_involved_in:
- id: GO:0017148
label: negative regulation of translation
- id: GO:0016071
label: mRNA metabolic process
- molecular_function:
id: GO:0003724
label: RNA helicase activity
description: CGH-1 functions in translational repression as a P-body
component, inhibiting translation of target mRNAs. This is a conserved
function of DDX6 family helicases.
locations:
- id: GO:0000932
label: P-body
directly_involved_in:
- id: GO:0017148
label: negative regulation of translation
- id: GO:0033962
label: P-body assembly
- molecular_function:
id: GO:0003724
label: RNA helicase activity
description: CGH-1 protects developing oocytes from physiological germline
apoptosis. Loss of cgh-1 was the first identified stimulus that triggers
excessive germline apoptosis. This is a unique and defining function of
CGH-1 in C. elegans germline development.
locations:
- id: GO:0043186
label: P granule
directly_involved_in:
- id: GO:0043066
label: negative regulation of apoptotic process
- id: GO:0007276
label: gamete generation
proposed_new_terms: []
suggested_questions:
- question: What are the specific mRNA targets of CGH-1-mediated translational
repression?
- question: How does CGH-1 coordinate with the apoptosis pathway to protect
developing oocytes?
- question: What is the structural basis for CGH-1's interaction with CAR-1?
- question: Does CGH-1 function differently in P granules vs P-bodies?
suggested_experiments:
- description: CLIP-seq or related methods to identify direct mRNA targets of
CGH-1
hypothesis: CGH-1 binds specific maternal mRNAs to protect them from
degradation and regulate their translation
- description: Structure-function analysis of CGH-1 helicase activity vs RNA
binding in apoptosis protection
hypothesis: CGH-1's anti-apoptotic function may require RNA binding but not
necessarily helicase activity
- description: Live imaging of CGH-1 dynamics between P granules and P-bodies
during oocyte development
hypothesis: CGH-1 shuttles between P granules and P-bodies to coordinate mRNA
fate during oogenesis
tags:
- caeel-p-granules