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WormBase Tree Display for Variation: WBVar00090710

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Name Class

WBVar00090710EvidencePaper_evidenceWBPaper00027336
NamePublic_namen3441
Other_nameCE46695:p.Trp534Ter
Y71G12B.9b.1:c.1601G>A
CE39067:p.Trp534Ter
Y71G12B.9a.1:c.1601G>A
HGVSgCHROMOSOME_I:g.1763192G>A
Sequence_detailsSMapS_parentSequenceY71G12B
Flanking_sequencescaagtaccggccttccggcaacagtcagatggaagcaattccaccgccaaaaaatccgaa
Mapping_targetY71G12B
Type_of_mutationSubstitutiongaPaper_evidenceWBPaper00027336
SeqStatusSequenced
Variation_typeAllele
OriginSpeciesCaenorhabditis elegans
StrainWBStrain00027427
LaboratoryMT
StatusLive
AffectsGeneWBGene00022149
TranscriptY71G12B.9b.1VEP_consequencestop_gained
VEP_impactHIGH
HGVScY71G12B.9b.1:c.1601G>A
HGVSpCE46695:p.Trp534Ter
cDNA_position1601
CDS_position1601
Protein_position534
Exon_number5/5
Codon_changetGg/tAg
Amino_acid_changeW/*
Y71G12B.9a.1VEP_consequencestop_gained
VEP_impactHIGH
HGVScY71G12B.9a.1:c.1601G>A
HGVSpCE39067:p.Trp534Ter
cDNA_position1602
CDS_position1601
Protein_position534
Exon_number6/10
Codon_changetGg/tAg
Amino_acid_changeW/*
Interactor (13)
GeneticsInterpolated_map_positionI-12.9068
DescriptionPhenotypeWBPhenotype:0000114Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"In the absence of lin-65 and met-2, many cco-1-regulated genes exhibited wide variance in expression patterns and failed to become significantly changed from their expression on empty vector. In fact, a majority of the gene expression changes (884 upregulated genes and 380 downregulated genes) induced by cco-1 RNAi were abrogated in lin-65 or met-2 mutant animals (Figures 5A, S6A, and S6B; Table S2)"Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_assayGenotypecco-1(RNAi)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBPhenotype:0000679Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"To understand the interdependency of DVE-1 and LIN-65 in response to mitochondrial stress, we performed epistasis analysis in lin-65(n3441) animals carrying a dve-1p::dve-1::gfp reporter and fed cco-1 RNAi. Strikingly, lin-65 mutants abolished DVE-1::GFP nuclear accumulation in cco-1 RNAi-treated animals (Figure 4B). This phenotype was rescued by expression of lin-65 with either its own promoter or an intestinal-specific gly-19 promoter (Figures S4A and S4B)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
"In comparison, the intensity of nuclear DVE-1::GFP signal decreased in both lin-65 and met-2 animals fed cco-1 RNAi (Figure S4D) and fewer cells contained detectable DVE-1::GFP puncta (Figures 4E and S4D)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Rescued_by_transgeneWBTransgene00023665
EQ_annotationsGO_termGO:0034514PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
GO:0005634PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_assayGenotypezcIs39 [dve-1p::dve-1::gfp]; cco-1(RNAi)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBPhenotype:0001171Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"Both lin-65 and met-2 animals are short-lived under normal conditions." (Figure 6C)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
"As predicted, both lin-65(n3441) and met-2(ok2307) only partially suppressed the lifespan extension of cco-1 RNAi-treated animals (Figures 6C and 6D; Table S1)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_assayGenotypecco-1(RNAi)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBPhenotype:0001276Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
RemarkVC1, VC2, VC3, and VC6 ectopically express the VC4/VC5-specific gene unc-4; uIs45 [unc-4p::MDM2::GFP] was used as the reporter for unc-4.Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
EQ_annotationsAnatomy_termWBbt:0004621PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBbt:0004619PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBbt:0004618PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBbt:0004611PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
Phenotype_assayGenotypeuIs45 [unc-4p::MDM2::GFP]Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBPhenotype:0001278Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"Using the characterized lin-65 mutant allele n3441, we confirmed that lin-65 is required for the UPRmt in response to rgef-1p::Q40::yfp expression (Figure 1A)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
"Western blot analyses confirmed the loss of hsp-6p::gfp expression in lin-65 mutants, while PolyQ expression remained unaffected (Figure 1B)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
"The lin-65 mutation strongly attenuated the upregulation of the UPRmt in animals fed RNAi targeting the cytochrome c oxidase-1 subunit Vb/COX4 of the electron transport chain, cco-1, or animals fed RNAi targeting phb-2, the ortholog of prohibitin PHB2 (Figure S1B)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
"To further explore the role of LIN-65 in mediating the DVE-1 nuclear signal, we asked if LIN-65 also plays a role in regulating DVE-1 protein levels. Western blot analyses confirmed that DVE-1::GFP protein levels decreased in lin-65 animals when cco-1 RNAi was applied (Figure 4D)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Rescued_by_transgeneWBTransgene00023665
EQ_annotationsGO_termGO:0034514PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_assayGenotypezcs13 [hsp-6p::GFP]; rmIs101 [rgef-1p::Q40::YFP]Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
zcs13 [hsp-6p::GFP]Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
zcIs13 [hsp-6p::GFP]; cco-1(RNAi)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
zcIs13 [hsp-6p::GFP]; phb-2(RNAi)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
zcIs39 [dve-1p::dve-1::gfp]; cco-1(RNAi)Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBPhenotype:0001510Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
RemarkVC1, VC2, VC3, and VC6 ectopically express the VC4/VC5-specific gene unc-4; uIs45 [unc-4p::MDM2::GFP] was used as the reporter for unc-4.Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
EQ_annotationsAnatomy_termWBbt:0004621PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBbt:0004619PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBbt:0004618PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBbt:0004611PATO:0000460Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
Phenotype_assayGenotypeuIs45 [unc-4p::MDM2::GFP]Paper_evidenceWBPaper00044613
Curator_confirmedWBPerson24243
WBPhenotype:0001567Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"Surprisingly, we also observed striking changes in chromatin structure in intestinal nuclei on mitochondrial stress. The intestinal nuclei appeared smaller and much more condensed in cco-1 RNAi-treated animals, while in contrast, met-2 and lin-65 animals had enlarged nuclei and a loose chromatin structure that remained relatively loose in structure even after mitochondrial stress was induced by cco-1 RNAi (Figure 3A)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
EQ_annotationsAnatomy_termWBbt:0005792PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
GO_termGO:0005634PATO:0000586Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBPhenotype:0002078Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"We therefore examined whether animals with reduced ETC function exhibit changes in methylation patterns. To this end, we performed immunohistochemistry against H3K9me2 marks in germlines carrying mutations in met-2 or lin-65. In agreement with previous reports, H3K9me2 level was almost undetectable in met-2 mutants (Figure S3A). Intriguingly, however, we found that lin-65 mutation severely reduced H3K9me2 levels as well (Figure S3A)... met-2 or lin-65 mutations also abolished or severely reduced H3K9me2 methylation in intestinal cells under basal or mitochondrial stress conditions compared to wild-type animals (Figures 3A and 3B)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
EQ_annotationsAnatomy_termWBbt:0005784PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBbt:0005772PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_not_observedWBPhenotype:0000306Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"We crossed the lin-65(n3441) mutation into animals harboring a reporter (hsp-4p::gfp) for an ER-specific stress response, the UPRer (Ron and Walter, 2007). Animals were then treated with the ER-specific stressor tunicamycin, which blocks N-linked glycosylation and induces the UPRer (Heifetz et al., 1979). lin-65 did not affect the upregulation of the hsp-4p::gfp reporter by tunicamycin (Figure S1C)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
"Similarly, we observed that lin-65 animals were fully capable of a cytoplasmic response to a heat shock through upregulation of an hsp-16.2p::gfp reporter (Figure S1D) (Link et al., 1999)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0030968PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
GO:0009408PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_assayTreatment"Synchronized day 1 of adulthood animals were placed at 34C for 20 min and allowed to recover for 6 hr prior to imaging."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
GenotypezcIs4 [hsp-4p::GFP]Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
dvIs70 [hsp-16.2p::GFP]Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
WBPhenotype:0001485Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Remark"We crossed the lin-65(n3441) mutation into animals harboring a reporter (hsp-4p::gfp) for an ER-specific stress response, the UPRer (Ron and Walter, 2007). Animals were then treated with the ER-specific stressor tunicamycin, which blocks N-linked glycosylation and induces the UPRer (Heifetz et al., 1979). lin-65 did not affect the upregulation of the hsp-4p::gfp reporter by tunicamycin (Figure S1C)."Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0030968PATO:0000460Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
Phenotype_assayGenotypezcIs4 [hsp-4p::GFP]Paper_evidenceWBPaper00050412
Curator_confirmedWBPerson2987
ReferenceWBPaper00027336
WBPaper00044613
WBPaper00050412
MethodSubstitution_allele