car-1

Existing Annotations Review

Core Functions

CAR-1 is an mRNA-binding protein that functions in post-transcriptional regulation of maternally loaded mRNAs. It directly binds RNA through its atypical Sm domain and RGG box. CAR-1 forms an RNA-dependent complex with CGH-1 (DDX6 homolog) and CEY-2, functioning in P-body and P-granule mediated mRNA regulation. It is essential for embryonic cytokinesis and regulates physiological germline apoptosis.

Molecular Function:

mRNA binding

Directly Involved In:

mitotic cytokinesis negative regulation of apoptotic process negative regulation of translation

Cellular Locations:

P granule P-body

In Complex:

ribonucleoprotein complex

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

CAR-1 is orthologous to LSM14 family proteins across eukaryotes

GO_REF:0000043

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

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:16221731

A conserved RNA-protein complex component involved in physiological germline apoptosis regulation in C. elegans.

CAR-1 associates with CGH-1 and Y-box proteins in a conserved germline RNP complex
The CGH-1/CAR-1 interaction is conserved in Drosophila oocytes
car-1(RNAi) increases physiological germline apoptosis
CAR-1 is critical for oogenesis

PMID:16247027

A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans.

CAR-1 contains an atypical Sm domain and RGG box that bind RNA
CAR-1 forms an RNA-dependent complex with CGH-1 and CEY-2
CAR-1 localizes to P-granules and smaller cytoplasmic particles
The Sm domain is essential for CAR-1 function but not localization
CAR-1 depletion causes failure of interzonal microtubule bundle formation
CAR-1 depletion prevents AIR-2 and ZEN-4 targeting to spindle midzone
CGH-1 controls CAR-1 particle localization

PMID:16267265

CAR-1, a protein that localizes with the mRNA decapping component DCAP-1, is required for cytokinesis and ER organization in Caenorhabditis elegans embryos.

CAR-1 colocalizes with DCAP-1 in P-bodies
CAR-1 localizes to P-granules
car-1 inhibition causes late cytokinesis failures
Spindle midzone fails to form in car-1 depleted embryos
ER organization is disrupted in car-1 depleted embryos

PMID:18430416

Involvement of HMG-12 and CAR-1 in the cdc-48.1 expression of Caenorhabditis elegans.

CAR-1 was identified as binding to Element B in cdc-48.1 promoter
car-1(RNAi) decreases cdc-48.1 and cdc-48.2 expression in embryos

PMID:18515547

C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis.

LARP-1 colocalizes with P bodies containing CAR-1

PMID:18695046

Maternal mRNAs are regulated by diverse P body-related mRNP granules during early Caenorhabditis elegans development.

Loss of CAR-1 causes ectopic GLP-1 protein expression in oocytes while glp-1 mRNA levels remain unchanged, indicating CAR-1 controls glp-1 translation rather than mRNA production or stability

"glp-1 mRNA levels were similar in car-1(tm1753) mutant and wild-type animals, which supports CAR-1 control of glp-1 translation rather than mRNA production or stability"
CAR-1 promotes PUF-dependent translational repression of glp-1 during late oogenesis

PMID:24367695

PAB-1, a Caenorhabditis elegans poly(A)-binding protein, regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1.

PAB-1 colocalizes with CAR-1 in P-granules and P-bodies
PAB-1, CGH-1, and CAR-1 interact in mRNA metabolism regulation
CGH-1 controls CAR-1 localization; CAR-1 does not control CGH-1 localization
PAB-1 affects CGH-1 and CAR-1 localization

PMID:25261697

Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.

CAR-1 is a component of OMA-1 ribonucleoprotein particles
OMA RNPs contain translational repressors and activators

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

Falcon (Edison Scientific) deep research report on C. elegans car-1 (Q9XW17)

CAR-1 is a conserved LSM14/Scd6/Rap55-family RNA-binding protein that partitions into cytoplasmic RNP condensates (P-bodies/P-body-like foci and germ granules) and acts as an adaptor/scaffold rather than an enzyme.

"CAR-1 is not an enzyme; it is best annotated as an **RNA-binding mRNP assembly/adaptor protein**"
CAR-1 directly binds RNA, with its RGG region binding poly(U) in vitro and an N-terminal Lsm domain consistent with the LSM14/Scd6/Rap55 family.

"RGG region binds poly(U) in vitro, supporting direct RNA-binding capacity."
CAR-1 promotes translational repression of specific maternal mRNAs, including PUF-dependent repression of glp-1 in oogenesis.

"In the germline/oogenesis, CAR-1 promotes PUF-dependent repression of the Notch-like receptor mRNA **glp-1**, and car-1 depletion elevates GLP-1 protein while glp-1 mRNA levels remain similar, consistent with primary control at the translation level."
CAR-1 is required for late embryonic cytokinesis and ER organization; depletion causes furrow regression and disrupted spindle midzone.

"CAR-1 is required for late cytokinesis/scission; depletion causes cleavage furrows to ingress then regress and disrupts membrane accumulation and spindle midzone organization"
In neurons, CAR-1/LSM14 represses micu-1 to modulate mitochondrial Ca2+ dynamics and acts as a cell-intrinsic inhibitor of PLM axon regrowth.

"represses neuronal **micu-1**, thereby modulating mitochondrial Ca2+ uptake dynamics after axotomy and acting as a cell-intrinsic inhibitor of PLM axon regrowth."
CAR-1 contributes a scaffold role to decapping condensates; in edc-3(0);edc-4(0) embryos car-1 RNAi reduces DCAP-2 foci 2-4.5-fold.

"car-1 RNAi (64% knockdown) in this background reduces DCAP-2 foci 2–4.5-fold, supporting a scaffold role for CAR-1 in alternative condensate frameworks when canonical scaffolds are absent."
CAR-1 organizes condensate-condensate interactions supporting piRNA-dependent transgenerational silencing, promoting CGH-1 perinuclear localization and its binding to PRG-1/WAGO-1.

"CAR-1 promotes CGH-1 perinuclear localization/condensate formation, and CAR-1 depletion reduces CGH-1 binding to PRG-1 and WAGO-1"

Suggested Experiments

Experiment: CLIP-seq or RIP-seq to identify direct CAR-1 mRNA targets in embryos and germline.

Experiment: Determine whether CAR-1's effect on cdc-48.1 expression is at the transcriptional or post-transcriptional level.

Experiment: Characterize the specific mRNAs regulated by CAR-1 that are required for interzonal microtubule bundle formation.

Deep Research

Falcon

(car-1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 39 citations 2 artifacts 2026-05-30T10:38:10.873542

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000032 The requested visual content is found in Figures 1, 4, and 5. - **Figure 4 (Page 6)**: Shows CAR-1 localization. Panel **A** illust (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Functional Annotation of C. elegans car-1 (UniProt Q9XW17; ORF Y18D10A.17)

Executive summary

car-1 encodes a conserved LSM14/Scd6/Rap55-family RNA-binding protein that partitions into cytoplasmic ribonucleoprotein (RNP) condensates (P-bodies/P-body-like foci and germ granules) and coordinates post-transcriptional control of specific mRNAs. Rather than catalyzing a biochemical reaction, CAR-1 acts as an adaptor/scaffold that (i) promotes translational repression and mRNP granule association, (ii) interfaces with mRNA decapping/decay factors in a context-dependent manner, and (iii) couples RNA regulation to membrane/ER organization and developmental programs including embryonic cytokinesis, oogenesis, neuronal axon regeneration, and germline small-RNA inheritance. Foundational cell-biological evidence established CAR-1 colocalization with the decapping cofactor DCAP-1 and requirements for cytokinesis and ER organization in embryos, while recent work (2023–2024) positions CAR-1 as a key organizer at the P-body–germ-granule interface in piRNA-dependent transgenerational silencing and as a regulated target/participant of embryonic mRNA clearance pathways that specialize decapping condensates. (squirrell2006car1aprotein pages 1-2, decker2006car1andtrailer pages 3-4, du2023condensatecooperativityunderlies pages 5-6, vidya2024edc3andedc4 pages 9-12, vidya2024edc3andedc4 pages 5-9)

Gene/protein identity verification (mandatory)

Multiple independent sources explicitly match the requested target: C. elegans CAR-1 is a member of the LSM14/Scd6/Rap55 family of Sm-like RNA-binding proteins. Squirrell et al. reported a predicted ~340-aa glycine-rich protein with clustered RGG motifs (RGG box) and clear homologs (Xenopus RAP55, yeast Scd6p/Lsm13p, Drosophila Trailer Hitch), consistent with UniProt Q9XW17 family assignment. (squirrell2006car1aprotein pages 1-2) Decker & Parker classified CAR-1 as the C. elegans Scd6 ortholog, noting an N-terminal Lsm domain (family feature) and poly(U) binding by the RGG region. (decker2006car1andtrailer pages 2-3, decker2006car1andtrailer pages 1-2) Later work explicitly referred to CAR-1 as CAR-1/LSM14. (tang2020themrnadecay pages 1-3, vidya2024edc3andedc4 pages 1-5)

1) Key concepts and definitions (current understanding)

1.1 LSM14/Scd6/Rap55 proteins (CAR-1)

LSM14-family proteins are conserved RNA-associated factors enriched in cytoplasmic mRNP granules. Mechanistically, they are frequently discussed as components of translation repression complexes and P-bodies, with conserved low-complexity/RGG regions enabling RNA binding and assembly into higher-order RNPs. (decker2006car1andtrailer pages 2-3, decker2006car1andtrailer pages 1-2)

1.2 Processing bodies (P-bodies) and germ granules

P-bodies are cytoplasmic condensates enriched in translationally repressed mRNAs and factors for mRNA turnover (decapping and 5′→3′ decay). A key expert framing is that P-bodies can act as sites where mRNAs are held in a repressed state and later returned to translation or routed to decay, and that granule aggregation may support mRNA transport and maintenance of translational repression. (decker2006car1andtrailer pages 1-2, decker2006car1andtrailer pages 4-4)
In C. elegans, CAR-1 localizes both to P granules (germ granules) and to DCAP-1-positive cytoplasmic foci interpreted as P-body-like structures. (squirrell2006car1aprotein pages 6-7)

1.3 Condensate “specialization” and inter-condensate coupling

Recent C. elegans work emphasizes that multiple condensate types (P-bodies, germ granules, stress granules) can coexist and interact, and that developmentally regulated clearance of mRNAs encoding condensate scaffolds helps shape condensate composition across embryogenesis. (vidya2024edc3andedc4 pages 1-5, vidya2024edc3andedc4 pages 19-23)

2) Functional annotation: molecular function, localization, and pathways

2.1 Molecular function (what CAR-1 does)

CAR-1 is not an enzyme; it is best annotated as an RNA-binding mRNP assembly/adaptor protein that promotes translational repression and can channel mRNAs toward, or away from, decapping/decay depending on developmental context.

Direct/functional evidence for RNA-binding and repression: CAR-1’s RGG region binds poly(U) in vitro, supporting direct RNA-binding capacity. (decker2006car1andtrailer pages 1-2) In the germline/oogenesis, CAR-1 promotes PUF-dependent repression of the Notch-like receptor mRNA glp-1, and car-1 depletion elevates GLP-1 protein while glp-1 mRNA levels remain similar, consistent with primary control at the translation level. (noble2008maternalmrnasare pages 8-9)

Context-dependent relationship to decapping/decay: CAR-1 colocalizes with decapping machinery and can be described as an mRNA decay-associated factor in neurons; in other settings CAR-1 participates in complexes that repress translation and can prevent decapping/decay. (tang2020themrnadecay pages 3-4, vidya2024edc3andedc4 pages 1-5)

2.2 Subcellular localization (where CAR-1 acts)

CAR-1 localizes broadly in cytoplasm but concentrates in at least two granule populations: (i) PGL-1-positive P granules and (ii) smaller DCAP-1-positive cytoplasmic foci; figure evidence from Squirrell et al. captures CAR-1 colocalization with both PGL-1 and DCAP-1. (squirrell2006car1aprotein pages 6-7, squirrell2006car1aprotein media 35d21d13)
CAR-1 is also functionally coupled to the endoplasmic reticulum (ER) in embryos, where depletion disrupts ER reticulation and spindle/midzone-associated ER, consistent with an ER-linked mRNP/granule function. (decker2006car1andtrailer pages 3-4)
In neurons, CAR-1 forms cytoplasmic puncta in cell bodies that fully colocalize with CGH-1/DDX6 and partially with DCAP-1, suggesting heterogeneous CAR-1 granules with variable decapping factor content. (tang2020themrnadecay pages 3-4)

2.3 Biological processes and pathways

Embryogenesis: cytokinesis and ER organization. CAR-1 is required for late cytokinesis/scission; depletion causes cleavage furrows to ingress then regress and disrupts membrane accumulation and spindle midzone organization, accompanied by ER morphology defects. (squirrell2006car1aprotein pages 1-2, decker2006car1andtrailer pages 3-4, squirrell2006car1aprotein media cc00f993)

Germline/oogenesis: maternal mRNA control. CAR-1 contributes to stage-specific translational repression of maternal mRNAs, including glp-1, and genetically interacts with PUF proteins, supporting a model where CAR-1 acts with sequence-specific RBPs to enforce developmental timing of translation. (noble2008maternalmrnasare pages 7-8, noble2008maternalmrnasare pages 8-9)

Neurons: axon regeneration via mitochondrial Ca2+ regulation. Tang et al. describe CAR-1/LSM14 as a translational repressor/mRNA decay factor that represses neuronal micu-1, thereby modulating mitochondrial Ca2+ uptake dynamics after axotomy and acting as a cell-intrinsic inhibitor of PLM axon regrowth. (tang2020themrnadecay pages 1-3, tang2020themrnadecay pages 3-4)

Germline inheritance: piRNA-dependent transgenerational silencing. Du et al. (2023) identify CAR-1 as a P-body component required for proper CGH-1/DDX6 perinuclear condensates and for robust interaction of CGH-1 with piRNA pathway factors (e.g., PRG-1, WAGO-1); car-1 RNAi disperses CGH-1 and reduces these interactions, impairing piRNA reporter silencing readouts. (du2023condensatecooperativityunderlies pages 5-6, du2023condensatecooperativityunderlies pages 24-29)

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2023: condensate cooperativity in transgenerational gene silencing

A central 2023 advance is that CAR-1 is implicated in organizing condensate–condensate interactions at the cytoplasmic face of perinuclear germ granules: CAR-1 promotes CGH-1 perinuclear localization/condensate formation, and CAR-1 depletion reduces CGH-1 binding to PRG-1 and WAGO-1 and perturbs perinuclear localization of PRG-1/WAGO-4, linking CAR-1 to piRNA pathway architecture. (du2023condensatecooperativityunderlies pages 5-6, du2023condensatecooperativityunderlies pages 24-29)

3.2 2024: embryonic mRNA clearance and P-body specialization (EDC-3/EDC-4)

Vidya et al. (bioRxiv, 2024-03-04) report that decapping scaffolds EDC-3 and EDC-4 shape DCAP-2 condensates in embryos and promote timed clearance of mRNAs including car-1. (vidya2024edc3andedc4 pages 1-5, vidya2024edc3andedc4 pages 19-23)
Quantitatively, the authors show the DCAP-2 interactome changes markedly in edc-3(0);edc-4(0) embryos, with increased association to IFET-1, CAR-1, and CGH-1, and that car-1 RNAi (64% knockdown) in this background reduces DCAP-2 foci 2–4.5-fold, supporting a scaffold role for CAR-1 in alternative condensate frameworks when canonical scaffolds are absent. (vidya2024edc3andedc4 pages 9-12)

3.3 2024: oogenesis—ER morphology, phase transitions, and translational repression

Elaswad et al. (MBoC, 2024-10) identify CCT chaperonin and actin as inhibitors of ectopic RNA-binding protein condensation during oogenesis and connect ER sheet expansion to induction of condensates containing CAR-1. (elaswad2024thecctchaperonin pages 1-2, elaswad2024thecctchaperonin pages 11-13) They further link ectopic condensation of regulators including CAR-1 to translational derepression of a maternal mRNA readout (spn-4), with quantitative imaging of SPN-4::GFP increases upon cct-2 depletion. (elaswad2024thecctchaperonin pages 10-11)

4) Current applications and real-world implementations

4.1 CAR-1 as an experimental handle for mRNP granule biology in vivo

CAR-1’s robust granule localization across germline, embryo, and neurons makes it a practical marker and perturbation target to study: (i) condensate material properties and stress responses, (ii) coupling between RNA regulation and organelle organization (ER), and (iii) inter-condensate organization supporting small-RNA inheritance. Imaging work operationalized CAR-1 “condensation” by cortex granule counts, showing time-dependent increases under imaging stress (40% condensed at 11–20 min; 60–100% after >30 min), highlighting methodological implications for live imaging of condensates. (elaswad2022imagingassociatedstresscauses pages 7-8)

4.2 Translational relevance via conserved LSM14-family biology

The CAR-1 family is conserved (LSM14A/LSM14B in mammals), and expert framing posits Scd6/LSM14 proteins as conserved integrators of translational repression and mRNA storage/decay in P-bodies, sometimes associated with ER-linked local translation. (decker2006car1andtrailer pages 1-2, decker2006car1andtrailer pages 4-4)
In disease-relevant cell biology, a 2024 Nature Cell Biology paper isolated LSM14A-GFP+ P-bodies from leukemia cell lysates by particle sorting and performed RNA-seq, providing a real-world example where LSM14-family proteins enable biochemical purification of P-bodies to define disease-associated RNA sequestration programs. (squirrell2006car1aprotein media 35d21d13)

5) Expert opinions and analysis

A widely cited expert perspective is that aggregation of mRNPs into granules can facilitate mRNA transport and help maintain translational repression, and that P-bodies are dynamic sites where mRNAs can be stored for reactivation or routed to decay. This conceptual framework supports interpreting CAR-1 phenotypes (translation control, developmental timing, and context-dependent links to decapping) through a granule-centric model rather than a single linear decay pathway. (decker2006car1andtrailer pages 1-2)

6) Quantitative statistics and data highlights

Key quantitative findings supporting functional annotation include:

Embryogenesis/oogenesis genetic interaction penetrance: In combined car-1; puf-5 perturbations, high penetrance defects were reported (e.g., small oocytes 86% (n=36), yolk accumulation 84% (n=37), eggshell defects 90% (n=49), cytokinesis defects 98% (n=203)). (noble2008maternalmrnasare pages 7-8)
Neuronal regeneration statistics: CAR-1 loss enhances PLM axon regrowth with statistical significance (tests include Fisher’s exact and ANOVA; p-values reported as p<0.01/*p<0.001; n on the order of ≥100). (tang2020themrnadecay pages 3-4)
Embryonic P-body formation and CAR-1 scaffold contribution: Wild-type embryos reach ~250 DCAP-2 foci at 4–6-cell and up to ~1,000 by ~100-cell; in edc-3(0);edc-4(0) embryos, DCAP-2 association with CAR-1 increases (~2.0-fold), and car-1 RNAi reduces DCAP-2 foci 2–4.5-fold in that background. (vidya2024edc3andedc4 pages 5-9, vidya2024edc3andedc4 pages 9-12)
Stress/condensation frequency: CAR-1 condensation under imaging-associated stress was observed in 40% of worms by 11–20 min and 60–100% beyond 30 min. (elaswad2022imagingassociatedstresscauses pages 7-8)
Longevity/proteostasis via SUMOylation switch: CAR-1 is SUMOylated and IIS reduction lowers SUMOylated CAR-1 (~3-fold by MS); car-1 loss shortened lifespan (14.81±0.41 d vs 17.56±0.52 d), while SUMOylation-resistant CAR-1 K185R extended lifespan (22.51±0.60 d vs 14.70±0.59 d; ~53% increase; p<0.001). (moll2018theinsulinigfsignaling pages 2-3, moll2018theinsulinigfsignaling pages 6-8, moll2018theinsulinigfsignaling pages 3-6)

Evidence summary table

Aspect	Key findings (1-3 bullets)	Evidence	URL/DOI	Pub date
identity/domains	• car-1 in C. elegans encodes an LSM14/Rap55/Scd6-family Sm-like RNA-binding protein. • Protein features reported in primary literature include a glycine-rich C-terminus with clustered RGG motifs/RGG box; review literature notes N-terminal Lsm domain and RNA binding/poly(U) binding, consistent with UniProt family/domain assignment. • Homology links CAR-1 to RAP55, Trailer Hitch, Scd6 family proteins.	Squirrell 2006 showed CAR-1 is a predicted 340-aa protein with clustered RGG motifs and homologs including RAP55, Scd6p/Lsm13p and Trailer Hitch; Decker & Parker 2006 classified CAR-1 as a Scd6-family/Lsm protein with RNA-binding properties; Tang 2020 explicitly identified CAR-1 as CAR-1/LSM14; Vidya 2024 listed CAR-1 as LSm14 (squirrell2006car1aprotein pages 1-2, decker2006car1andtrailer pages 2-3, tang2020themrnadecay pages 1-3, vidya2024edc3andedc4 pages 1-5).	https://doi.org/10.1091/mbc.e05-09-0874; https://doi.org/10.1083/jcb.200601153; https://doi.org/10.1016/j.cub.2019.12.061; https://doi.org/10.1101/2024.03.04.583404	Jan 2006; Apr 2006; Mar 2020; Mar 2024
molecular function	• Functions primarily as an RNA-associated translational repressor / mRNP assembly factor rather than an enzyme. • Acts with CGH-1/DDX6 and can interface with mRNA decapping machinery (DCAP-1/DCAP-2), with context-dependent roles in either repressing translation and protecting mRNAs or promoting entry into decay pathways. • Regulates specific targets, including glp-1 mRNA in oogenesis and micu-1 in neurons.	Noble 2008 showed CAR-1 promotes repression of glp-1 during late oogenesis and that glp-1 mRNA levels can remain unchanged while GLP-1 protein rises after car-1 perturbation, supporting translational control; Tang 2020 showed CAR-1 binds mature mRNAs with CGH-1, colocalizes with decapping factors, and represses neuronal micu-1; Vidya 2024 reported CAR-1/CGH-1/IFET-1 complexes can repress translation and prevent decapping/decay in some developmental contexts while CAR-1 is also linked to higher-order decapping assemblies (noble2008maternalmrnasare pages 7-8, noble2008maternalmrnasare pages 8-9, tang2020themrnadecay pages 3-4, vidya2024edc3andedc4 pages 1-5).	https://doi.org/10.1083/jcb.200802128; https://doi.org/10.1016/j.cub.2019.12.061; https://doi.org/10.1101/2024.03.04.583404	Aug 2008; Mar 2020; Mar 2024
localization	• Localizes to cytoplasmic RNA granules, including P-granules/germ granules and smaller DCAP-1-positive cytoplasmic foci/P-body-like granules. • Has functional/physical links to the ER in embryos; neuronal CAR-1 forms cytoplasmic puncta with CGH-1 and partly with DCAP-1. • Recent imaging work supports CAR-1 as a regulated condensate component whose condensation increases under stress or oocyte arrest.	Squirrell 2006 showed GFP::CAR-1 colocalizes with PGL-1 in P-granules and with DCAP-1 in cytoplasmic foci, and linked CAR-1 depletion to ER disorganization; figure evidence confirms CAR-1/DCAP-1 foci and ER defects (squirrell2006car1aprotein pages 6-7, squirrell2006car1aprotein media 35d21d13). Tang 2020 found neuronal CAR-1 puncta fully colocalize with CGH-1 and partially with DCAP-1 (tang2020themrnadecay pages 3-4, tang2020themrnadecay pages 1-3). Elaswad 2022 quantified stress-induced CAR-1 condensation in germline/oocyte contexts (elaswad2022imagingassociatedstresscauses pages 7-8).	https://doi.org/10.1091/mbc.e05-09-0874; https://doi.org/10.1016/j.cub.2019.12.061; https://doi.org/10.1093/g3journal/jkac172	Jan 2006; Mar 2020; Jul 2022
biological processes	• Required for late cytokinesis and normal ER organization in embryos. • Contributes to maternal mRNA regulation/oogenesis, including repression of glp-1 and proper oocyte/embryo development. • Also functions in axon regeneration control via mitochondrial calcium regulation and in piRNA/transgenerational gene silencing through condensate organization.	Squirrell 2006 showed car-1 loss causes furrow regression, absent spindle midzone, and ER defects in embryos (squirrell2006car1aprotein pages 1-2, decker2006car1andtrailer pages 3-4). Noble 2008 linked CAR-1 to late-oogenesis repression of glp-1 and strong genetic interactions with puf-5 affecting oogenesis/embryogenesis (noble2008maternalmrnasare pages 7-8, noble2008maternalmrnasare pages 8-9). Tang 2020 identified CAR-1 as a cell-intrinsic inhibitor of axon regrowth through repression of micu-1 and modulation of mitochondrial Ca2+ dynamics (tang2020themrnadecay pages 3-4, tang2020themrnadecay pages 1-3). Du 2023 showed CAR-1 promotes CGH-1 interactions with piRNA factors and supports transgenerational silencing-related condensate organization (du2023condensatecooperativityunderlies pages 5-6, du2023condensatecooperativityunderlies pages 24-29).	https://doi.org/10.1091/mbc.e05-09-0874; https://doi.org/10.1083/jcb.200802128; https://doi.org/10.1016/j.cub.2019.12.061; https://doi.org/10.1016/j.celrep.2023.112859	Jan 2006; Aug 2008; Mar 2020; Aug 2023
recent developments 2023-2024	• 2023: CAR-1 emerged as a key P-body factor organizing interactions between P-bodies and perinuclear germ granules to support piRNA-dependent transgenerational silencing. • 2024: CAR-1 was implicated in embryonic mRNA clearance / P-body specialization via interactions with EDC-3/EDC-4 and the IFET-1/CAR-1/CGH-1 complex. • 2024: Oogenesis work connected CAR-1 condensation to ER morphology, CCT/actin, and maintenance of translational repression/oocyte quality.	Du 2023 showed car-1 RNAi disperses CGH-1 from perinuclear P bodies, reduces CGH-1 interactions with PRG-1/WAGO-1, and impairs piRNA reporter silencing (du2023condensatecooperativityunderlies pages 5-6, du2023condensatecooperativityunderlies pages 24-29). Vidya 2024 showed EDC-3 promotes clearance of car-1 mRNA and that CAR-1 helps scaffold DCAP-2 condensates when EDC-3/EDC-4 are absent (vidya2024edc3andedc4 pages 9-12, vidya2024edc3andedc4 pages 16-19, vidya2024edc3andedc4 pages 1-5). Elaswad 2024 linked CAR-1 ectopic condensation to CCT/actin depletion and expanded ER sheets during oogenesis (elaswad2024thecctchaperonin pages 11-13, elaswad2024thecctchaperonin pages 7-8, elaswad2024thecctchaperonin pages 1-2).	https://doi.org/10.1016/j.celrep.2023.112859; https://doi.org/10.1101/2024.03.04.583404; https://doi.org/10.1091/mbc.e24-05-0216	Aug 2023; Mar 2024; Oct 2024
quantitative stats/data	• Axon regeneration: car-1(0) increased PLM axon regrowth/growth-cone formation; analyses used n ≳100, with p < 0.01 to p < 0.001 depending on comparison. • Oogenesis/embryogenesis: in car-1; puf-5 perturbation, phenotype penetrance was high: small oocytes 86% (n=36), yolk accumulation 84% (n=37), eggshell defects 90% (n=49), cytokinesis defects 98% (n=203). • Recent datasets: car-1 RNAi reduced DCAP-2 foci 2- to 4.5-fold in edc-3(0);edc-4(0) embryos; car-1/car-1 mRNA increased ~1.4-fold in edc-3(0) and ~1.6-fold in edc-3(0);edc-4(0); imaging stress induced CAR-1 condensation in 40% of worms at 11-20 min and 60-100% after >30 min; CAR-1 K185R extended lifespan to 22.51 ± 0.60 d vs 14.70 ± 0.59 d WT and car-1 loss shortened lifespan to 14.81 ± 0.41 d vs 17.56 ± 0.52 d WT.	Tang 2020 reported significant regeneration phenotypes with Fisher’s exact test / ANOVA and large sample sizes (tang2020themrnadecay pages 3-4). Noble 2008 provided penetrance/sample-size values for combined car-1/puf-5 phenotypes (noble2008maternalmrnasare pages 7-8). Vidya 2024 quantified CAR-1-dependent DCAP-2 foci reduction and car-1 mRNA increases in edc mutants (vidya2024edc3andedc4 pages 9-12, vidya2024edc3andedc4 pages 16-19). Elaswad 2022 quantified stress-induced CAR-1 condensation frequencies (elaswad2022imagingassociatedstresscauses pages 7-8). Moll 2018 quantified lifespan and SUMOylation-linked CAR-1 effects (moll2018theinsulinigfsignaling pages 6-8, moll2018theinsulinigfsignaling pages 3-6).	https://doi.org/10.1016/j.cub.2019.12.061; https://doi.org/10.1083/jcb.200802128; https://doi.org/10.1101/2024.03.04.583404; https://doi.org/10.1093/g3journal/jkac172; https://doi.org/10.7554/eLife.38635	Mar 2020; Aug 2008; Mar 2024; Jul 2022; Nov 2018

Table: This table summarizes evidence-based functional annotation for C. elegans car-1/LSM14 (UniProt Q9XW17), covering identity, molecular function, localization, biology, recent 2023-2024 developments, and quantitative findings. It is limited to claims directly supported by the provided context IDs.

Notes on limitations

Despite targeted retrieval, directly accessible 2023–2024 review articles focusing specifically on C. elegans CAR-1 (as opposed to broader condensate/P-body reviews) were limited in the acquired corpus; therefore, expert commentary is primarily drawn from a classic mini-review (2006) and integrated with 2023–2024 primary studies. Claims in this report are restricted to those supported by the cited evidence.

Key primary sources (URLs + publication dates)

Squirrell JM et al. 2006-01. Molecular Biology of the Cell. “CAR-1 … required for cytokinesis and ER organization…” https://doi.org/10.1091/mbc.e05-09-0874 (squirrell2006car1aprotein pages 1-2)
Decker CJ & Parker R. 2006-04. J Cell Biol. “CAR-1 and Trailer hitch…” https://doi.org/10.1083/jcb.200601153 (decker2006car1andtrailer pages 2-3)
Noble SL et al. 2008-08. J Cell Biol. “Maternal mRNAs are regulated…” https://doi.org/10.1083/jcb.200802128 (noble2008maternalmrnasare pages 7-8)
Tang NH et al. 2020-03. Current Biology. “CAR-1/LSM14 regulates axon regeneration…” https://doi.org/10.1016/j.cub.2019.12.061 (tang2020themrnadecay pages 3-4)
Du Z et al. 2023-08. Cell Reports. “Condensate cooperativity underlies transgenerational gene silencing.” https://doi.org/10.1016/j.celrep.2023.112859 (du2023condensatecooperativityunderlies pages 5-6)
Vidya E et al. 2024-03. bioRxiv. “EDC-3 and EDC-4 regulate embryonic mRNA clearance…” https://doi.org/10.1101/2024.03.04.583404 (vidya2024edc3andedc4 pages 9-12)
Elaswad MT et al. 2024-10. Molecular Biology of the Cell. “CCT chaperonin and actin modulate the ER and RBP condensation…” https://doi.org/10.1091/mbc.e24-05-0216 (elaswad2024thecctchaperonin pages 11-13)
Moll L et al. 2018-11. eLife. “IIS modulates SUMOylation to regulate aging…” https://doi.org/10.7554/eLife.38635 (moll2018theinsulinigfsignaling pages 6-8)

References

(squirrell2006car1aprotein pages 1-2): Jayne M. Squirrell, Zachary T. Eggers, Nancy Luedke, Bonnie Saari, Andrew Grimson, Gary E. Lyons, Philip Anderson, and John G. White. Car-1, a protein that localizes with the mrna decapping component dcap-1, is required for cytokinesis and er organization incaenorhabditis elegansembryos. Jan 2006. URL: https://doi.org/10.1091/mbc.e05-09-0874, doi:10.1091/mbc.e05-09-0874. This article has 104 citations and is from a domain leading peer-reviewed journal.
(decker2006car1andtrailer pages 3-4): Carolyn J. Decker and Roy Parker. Car-1 and trailer hitch: driving mrnp granule function at the er? The Journal of Cell Biology, 173:159-163, Apr 2006. URL: https://doi.org/10.1083/jcb.200601153, doi:10.1083/jcb.200601153. This article has 52 citations.
(du2023condensatecooperativityunderlies pages 5-6): Zhenzhen Du, Kun Shi, Jordan S. Brown, Tao He, Wei-Sheng Wu, Ying Zhang, Heng-Chi Lee, and Donglei Zhang. Condensate cooperativity underlies transgenerational gene silencing. Cell Reports, 42:112859, Aug 2023. URL: https://doi.org/10.1016/j.celrep.2023.112859, doi:10.1016/j.celrep.2023.112859. This article has 27 citations and is from a highest quality peer-reviewed journal.
(vidya2024edc3andedc4 pages 9-12): Elva Vidya, Yasaman Jami-Alahmadi, Adarsh K. Mayank, Javeria Rizwan, Jia Ming Stella Xu, Tianhao Cheng, Rania Leventis, Nahum Sonenberg, James A. Wohlschlegel, Maria Vera, and Thomas F. Duchaine. Edc-3 and edc-4 regulate embryonic mrna clearance and biomolecular condensate specialization. bioRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.04.583404, doi:10.1101/2024.03.04.583404. This article has 8 citations.
(vidya2024edc3andedc4 pages 5-9): Elva Vidya, Yasaman Jami-Alahmadi, Adarsh K. Mayank, Javeria Rizwan, Jia Ming Stella Xu, Tianhao Cheng, Rania Leventis, Nahum Sonenberg, James A. Wohlschlegel, Maria Vera, and Thomas F. Duchaine. Edc-3 and edc-4 regulate embryonic mrna clearance and biomolecular condensate specialization. bioRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.04.583404, doi:10.1101/2024.03.04.583404. This article has 8 citations.
(decker2006car1andtrailer pages 2-3): Carolyn J. Decker and Roy Parker. Car-1 and trailer hitch: driving mrnp granule function at the er? The Journal of Cell Biology, 173:159-163, Apr 2006. URL: https://doi.org/10.1083/jcb.200601153, doi:10.1083/jcb.200601153. This article has 52 citations.
(decker2006car1andtrailer pages 1-2): Carolyn J. Decker and Roy Parker. Car-1 and trailer hitch: driving mrnp granule function at the er? The Journal of Cell Biology, 173:159-163, Apr 2006. URL: https://doi.org/10.1083/jcb.200601153, doi:10.1083/jcb.200601153. This article has 52 citations.
(tang2020themrnadecay pages 1-3): Ngang Heok Tang, Kyung Won Kim, Suhong Xu, Stephen M. Blazie, Brian A. Yee, Gene W. Yeo, Yishi Jin, and Andrew D. Chisholm. The mrna decay factor car-1/lsm14 regulates axon regeneration via mitochondrial calcium dynamics. Current Biology, 30:865-876.e7, Mar 2020. URL: https://doi.org/10.1016/j.cub.2019.12.061, doi:10.1016/j.cub.2019.12.061. This article has 34 citations and is from a highest quality peer-reviewed journal.
(vidya2024edc3andedc4 pages 1-5): Elva Vidya, Yasaman Jami-Alahmadi, Adarsh K. Mayank, Javeria Rizwan, Jia Ming Stella Xu, Tianhao Cheng, Rania Leventis, Nahum Sonenberg, James A. Wohlschlegel, Maria Vera, and Thomas F. Duchaine. Edc-3 and edc-4 regulate embryonic mrna clearance and biomolecular condensate specialization. bioRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.04.583404, doi:10.1101/2024.03.04.583404. This article has 8 citations.
(decker2006car1andtrailer pages 4-4): Carolyn J. Decker and Roy Parker. Car-1 and trailer hitch: driving mrnp granule function at the er? The Journal of Cell Biology, 173:159-163, Apr 2006. URL: https://doi.org/10.1083/jcb.200601153, doi:10.1083/jcb.200601153. This article has 52 citations.
(squirrell2006car1aprotein pages 6-7): Jayne M. Squirrell, Zachary T. Eggers, Nancy Luedke, Bonnie Saari, Andrew Grimson, Gary E. Lyons, Philip Anderson, and John G. White. Car-1, a protein that localizes with the mrna decapping component dcap-1, is required for cytokinesis and er organization incaenorhabditis elegansembryos. Jan 2006. URL: https://doi.org/10.1091/mbc.e05-09-0874, doi:10.1091/mbc.e05-09-0874. This article has 104 citations and is from a domain leading peer-reviewed journal.
(vidya2024edc3andedc4 pages 19-23): Elva Vidya, Yasaman Jami-Alahmadi, Adarsh K. Mayank, Javeria Rizwan, Jia Ming Stella Xu, Tianhao Cheng, Rania Leventis, Nahum Sonenberg, James A. Wohlschlegel, Maria Vera, and Thomas F. Duchaine. Edc-3 and edc-4 regulate embryonic mrna clearance and biomolecular condensate specialization. bioRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.04.583404, doi:10.1101/2024.03.04.583404. This article has 8 citations.
(noble2008maternalmrnasare pages 8-9): Scott L. Noble, Brittany L. Allen, Lai Kuan Goh, Kristen Nordick, and Thomas C. Evans. Maternal mrnas are regulated by diverse p body–related mrnp granules during early caenorhabditis elegans development. The Journal of Cell Biology, 182:559-572, Aug 2008. URL: https://doi.org/10.1083/jcb.200802128, doi:10.1083/jcb.200802128. This article has 148 citations.
(tang2020themrnadecay pages 3-4): Ngang Heok Tang, Kyung Won Kim, Suhong Xu, Stephen M. Blazie, Brian A. Yee, Gene W. Yeo, Yishi Jin, and Andrew D. Chisholm. The mrna decay factor car-1/lsm14 regulates axon regeneration via mitochondrial calcium dynamics. Current Biology, 30:865-876.e7, Mar 2020. URL: https://doi.org/10.1016/j.cub.2019.12.061, doi:10.1016/j.cub.2019.12.061. This article has 34 citations and is from a highest quality peer-reviewed journal.
(squirrell2006car1aprotein media 35d21d13): Jayne M. Squirrell, Zachary T. Eggers, Nancy Luedke, Bonnie Saari, Andrew Grimson, Gary E. Lyons, Philip Anderson, and John G. White. Car-1, a protein that localizes with the mrna decapping component dcap-1, is required for cytokinesis and er organization incaenorhabditis elegansembryos. Jan 2006. URL: https://doi.org/10.1091/mbc.e05-09-0874, doi:10.1091/mbc.e05-09-0874. This article has 104 citations and is from a domain leading peer-reviewed journal.
(squirrell2006car1aprotein media cc00f993): Jayne M. Squirrell, Zachary T. Eggers, Nancy Luedke, Bonnie Saari, Andrew Grimson, Gary E. Lyons, Philip Anderson, and John G. White. Car-1, a protein that localizes with the mrna decapping component dcap-1, is required for cytokinesis and er organization incaenorhabditis elegansembryos. Jan 2006. URL: https://doi.org/10.1091/mbc.e05-09-0874, doi:10.1091/mbc.e05-09-0874. This article has 104 citations and is from a domain leading peer-reviewed journal.
(noble2008maternalmrnasare pages 7-8): Scott L. Noble, Brittany L. Allen, Lai Kuan Goh, Kristen Nordick, and Thomas C. Evans. Maternal mrnas are regulated by diverse p body–related mrnp granules during early caenorhabditis elegans development. The Journal of Cell Biology, 182:559-572, Aug 2008. URL: https://doi.org/10.1083/jcb.200802128, doi:10.1083/jcb.200802128. This article has 148 citations.
(du2023condensatecooperativityunderlies pages 24-29): Zhenzhen Du, Kun Shi, Jordan S. Brown, Tao He, Wei-Sheng Wu, Ying Zhang, Heng-Chi Lee, and Donglei Zhang. Condensate cooperativity underlies transgenerational gene silencing. Cell Reports, 42:112859, Aug 2023. URL: https://doi.org/10.1016/j.celrep.2023.112859, doi:10.1016/j.celrep.2023.112859. This article has 27 citations and is from a highest quality peer-reviewed journal.
(elaswad2024thecctchaperonin pages 1-2): Mohamed T. Elaswad, Mingze Gao, Victoria E. Tice, Cora G. Bright, Grace M. Thomas, Chloe Munderloh, Nicholas J. Trombley, Christya N. Haddad, Ulysses G. Johnson, Ashley N. Cichon, and Jennifer A. Schisa. The cct chaperonin and actin modulate the er and rna-binding protein condensation during oogenesis and maintain translational repression of maternal mrna and oocyte quality. Molecular Biology of the Cell, Oct 2024. URL: https://doi.org/10.1091/mbc.e24-05-0216, doi:10.1091/mbc.e24-05-0216. This article has 4 citations and is from a domain leading peer-reviewed journal.
(elaswad2024thecctchaperonin pages 11-13): Mohamed T. Elaswad, Mingze Gao, Victoria E. Tice, Cora G. Bright, Grace M. Thomas, Chloe Munderloh, Nicholas J. Trombley, Christya N. Haddad, Ulysses G. Johnson, Ashley N. Cichon, and Jennifer A. Schisa. The cct chaperonin and actin modulate the er and rna-binding protein condensation during oogenesis and maintain translational repression of maternal mrna and oocyte quality. Molecular Biology of the Cell, Oct 2024. URL: https://doi.org/10.1091/mbc.e24-05-0216, doi:10.1091/mbc.e24-05-0216. This article has 4 citations and is from a domain leading peer-reviewed journal.
(elaswad2024thecctchaperonin pages 10-11): Mohamed T. Elaswad, Mingze Gao, Victoria E. Tice, Cora G. Bright, Grace M. Thomas, Chloe Munderloh, Nicholas J. Trombley, Christya N. Haddad, Ulysses G. Johnson, Ashley N. Cichon, and Jennifer A. Schisa. The cct chaperonin and actin modulate the er and rna-binding protein condensation during oogenesis and maintain translational repression of maternal mrna and oocyte quality. Molecular Biology of the Cell, Oct 2024. URL: https://doi.org/10.1091/mbc.e24-05-0216, doi:10.1091/mbc.e24-05-0216. This article has 4 citations and is from a domain leading peer-reviewed journal.
(elaswad2022imagingassociatedstresscauses pages 7-8): Mohamed T Elaswad, Chloe Munderloh, Brooklynne M Watkins, Katherine G Sharp, Elizabeth Breton, and Jennifer A Schisa. Imaging-associated stress causes divergent phase transitions of rna-binding proteins in the caenorhabditis elegans germ line. G3: Genes|Genomes|Genetics, Jul 2022. URL: https://doi.org/10.1093/g3journal/jkac172, doi:10.1093/g3journal/jkac172. This article has 11 citations.
(moll2018theinsulinigfsignaling pages 2-3): Lorna Moll, Noa Roitenberg, Michal Bejerano-Sagie, Hana Boocholez, Filipa Carvalhal Marques, Yuli Volovik, Tayir Elami, Atif Ahmed Siddiqui, Danielle Grushko, Adi Biram, Bar Lampert, Hana Achache, Tommer Ravid, Yonatan B Tzur, and Ehud Cohen. The insulin/igf signaling cascade modulates sumoylation to regulate aging and proteostasis in caenorhabditis elegans. eLife, Nov 2018. URL: https://doi.org/10.7554/elife.38635, doi:10.7554/elife.38635. This article has 26 citations and is from a domain leading peer-reviewed journal.
(moll2018theinsulinigfsignaling pages 6-8): Lorna Moll, Noa Roitenberg, Michal Bejerano-Sagie, Hana Boocholez, Filipa Carvalhal Marques, Yuli Volovik, Tayir Elami, Atif Ahmed Siddiqui, Danielle Grushko, Adi Biram, Bar Lampert, Hana Achache, Tommer Ravid, Yonatan B Tzur, and Ehud Cohen. The insulin/igf signaling cascade modulates sumoylation to regulate aging and proteostasis in caenorhabditis elegans. eLife, Nov 2018. URL: https://doi.org/10.7554/elife.38635, doi:10.7554/elife.38635. This article has 26 citations and is from a domain leading peer-reviewed journal.
(moll2018theinsulinigfsignaling pages 3-6): Lorna Moll, Noa Roitenberg, Michal Bejerano-Sagie, Hana Boocholez, Filipa Carvalhal Marques, Yuli Volovik, Tayir Elami, Atif Ahmed Siddiqui, Danielle Grushko, Adi Biram, Bar Lampert, Hana Achache, Tommer Ravid, Yonatan B Tzur, and Ehud Cohen. The insulin/igf signaling cascade modulates sumoylation to regulate aging and proteostasis in caenorhabditis elegans. eLife, Nov 2018. URL: https://doi.org/10.7554/elife.38635, doi:10.7554/elife.38635. This article has 26 citations and is from a domain leading peer-reviewed journal.
(vidya2024edc3andedc4 pages 16-19): Elva Vidya, Yasaman Jami-Alahmadi, Adarsh K. Mayank, Javeria Rizwan, Jia Ming Stella Xu, Tianhao Cheng, Rania Leventis, Nahum Sonenberg, James A. Wohlschlegel, Maria Vera, and Thomas F. Duchaine. Edc-3 and edc-4 regulate embryonic mrna clearance and biomolecular condensate specialization. bioRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.04.583404, doi:10.1101/2024.03.04.583404. This article has 8 citations.
(elaswad2024thecctchaperonin pages 7-8): Mohamed T. Elaswad, Mingze Gao, Victoria E. Tice, Cora G. Bright, Grace M. Thomas, Chloe Munderloh, Nicholas J. Trombley, Christya N. Haddad, Ulysses G. Johnson, Ashley N. Cichon, and Jennifer A. Schisa. The cct chaperonin and actin modulate the er and rna-binding protein condensation during oogenesis and maintain translational repression of maternal mrna and oocyte quality. Molecular Biology of the Cell, Oct 2024. URL: https://doi.org/10.1091/mbc.e24-05-0216, doi:10.1091/mbc.e24-05-0216. This article has 4 citations and is from a domain leading peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

noble2008maternalmrnasare pages 8-9
tang2020themrnadecay pages 3-4
elaswad2024thecctchaperonin pages 10-11
elaswad2022imagingassociatedstresscauses pages 7-8
noble2008maternalmrnasare pages 7-8
du2023condensatecooperativityunderlies pages 5-6
elaswad2024thecctchaperonin pages 11-13
moll2018theinsulinigfsignaling pages 6-8
tang2020themrnadecay pages 1-3
du2023condensatecooperativityunderlies pages 24-29
elaswad2024thecctchaperonin pages 1-2
moll2018theinsulinigfsignaling pages 2-3
moll2018theinsulinigfsignaling pages 3-6
elaswad2024thecctchaperonin pages 7-8
https://doi.org/10.1091/mbc.e05-09-0874;
https://doi.org/10.1083/jcb.200601153;
https://doi.org/10.1016/j.cub.2019.12.061;
https://doi.org/10.1101/2024.03.04.583404
https://doi.org/10.1083/jcb.200802128;
https://doi.org/10.1093/g3journal/jkac172
https://doi.org/10.1016/j.celrep.2023.112859
https://doi.org/10.1016/j.celrep.2023.112859;
https://doi.org/10.1101/2024.03.04.583404;
https://doi.org/10.1091/mbc.e24-05-0216
https://doi.org/10.1093/g3journal/jkac172;
https://doi.org/10.7554/eLife.38635
https://doi.org/10.1091/mbc.e05-09-0874
https://doi.org/10.1083/jcb.200601153
https://doi.org/10.1083/jcb.200802128
https://doi.org/10.1016/j.cub.2019.12.061
https://doi.org/10.1091/mbc.e05-09-0874,
https://doi.org/10.1083/jcb.200601153,
https://doi.org/10.1016/j.celrep.2023.112859,
https://doi.org/10.1101/2024.03.04.583404,
https://doi.org/10.1016/j.cub.2019.12.061,
https://doi.org/10.1083/jcb.200802128,
https://doi.org/10.1091/mbc.e24-05-0216,
https://doi.org/10.1093/g3journal/jkac172,
https://doi.org/10.7554/elife.38635,

📄 View Raw YAML

id: Q9XW17
gene_symbol: car-1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: CAR-1 (Cytokinesis, Apoptosis, RNA-associated) is the C. elegans 
  ortholog of LSM14/Scd6 family proteins. It contains an N-terminal atypical Sm 
  domain that directly binds RNA, central DFDF/FFD/TFG motifs, and a C-terminal 
  RGG box. CAR-1 is a key component of both P-bodies (cytoplasmic mRNA 
  processing bodies) and P granules (germline-specific ribonucleoprotein 
  particles). It forms an RNA-dependent complex with the DEAD-box RNA helicase 
  CGH-1 (DDX6 ortholog) and the Y-box protein CEY-2, functioning in 
  post-transcriptional regulation of maternally loaded mRNAs. CAR-1 is essential
  for embryonic cytokinesis, where it is required for formation of interzonal 
  microtubule bundles during anaphase. It also regulates physiological germline 
  apoptosis, with car-1 depletion leading to increased germ cell death. The 
  protein localizes dynamically to P granules that concentrate in germline 
  precursors and to smaller cytoplasmic P-body particles present in all cells of
  early embryos.
existing_annotations:
  - term:
      id: GO:0000932
      label: P-body
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CAR-1 is a well-established P-body component. Multiple IDA 
        annotations support P-body localization (PMID:16267265, PMID:18515547, 
        PMID:24367695). CAR-1 colocalizes with DCAP-1, the mRNA decapping 
        component, in cytoplasmic foci that are characteristic of P-bodies 
        (PMID:16267265).
      action: ACCEPT
      reason: IBA annotation is fully supported by experimental evidence. CAR-1
        localizes with the mRNA decapping component DCAP-1 (PMID:16267265) and
        localizes to germline P bodies (PMID:18515547). P-body localization is
        central to CAR-1 function.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            CAR-1 localizes both to **P granules (germ granules)** and to **DCAP-1-positive cytoplasmic foci** interpreted as P-body-like structures.
          reference_section_type: RESULTS
  - term:
      id: GO:0003729
      label: mRNA binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CAR-1 contains an atypical Sm domain at its N-terminus that 
        directly binds RNA. The Sm domain and RGG box both bind to 
        poly(U)-sepharose beads in vitro (PMID:16247027). The Sm domain is 
        essential for CAR-1 function but not localization.
      action: ACCEPT
      reason: IBA annotation is well-supported. CAR-1 is a predicted RNA-binding
        protein with demonstrated RNA binding activity. The annotation is
        appropriately specific as CAR-1 functions in mRNA metabolism through
        P-body and P-granule complexes. Falcon deep research confirms direct
        poly(U) binding by the RGG region and an N-terminal Lsm domain consistent
        with the LSM14/Scd6/Rap55 family assignment.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            RGG region binds poly(U) in vitro, supporting direct RNA-binding capacity.
          reference_section_type: RESULTS
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            an N-terminal Lsm domain (family feature) and **poly(U) binding** by the RGG region
          reference_section_type: RESULTS
  - term:
      id: GO:0033962
      label: P-body assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CAR-1 is a core P-body component, but evidence suggests CGH-1 
        controls CAR-1 localization and P-body/particle formation rather than 
        CAR-1 driving assembly. In cgh-1 mutants, CAR-1 forms aberrant bar-like 
        structures (PMID:16247027, PMID:24367695).
      action: ACCEPT
      reason: |-
        IBA annotation is reasonable given CAR-1's conserved role as a
        P-body component. While CGH-1 appears more upstream in controlling
        particle assembly, CAR-1 is required for proper P-body function and its
        depletion affects RNP organization. Falcon deep research adds direct
        support for a scaffold contribution: in edc-3(0);edc-4(0) embryos
        lacking canonical decapping scaffolds, car-1 RNAi reduces DCAP-2 foci
        2-4.5-fold.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            car-1 RNAi (64% knockdown) in this background reduces DCAP-2 foci 2–4.5-fold, supporting a scaffold role for CAR-1 in alternative condensate frameworks when canonical scaffolds are absent.
          reference_section_type: RESULTS
  - term:
      id: GO:0034063
      label: stress granule assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: While CAR-1 is a known component of RNP granules that share 
        features with stress granules, direct evidence for CAR-1 involvement in 
        stress granule assembly in C. elegans is limited. The annotation is 
        based on phylogenetic inference from yeast Scd6 and other orthologs.
      action: KEEP_AS_NON_CORE
      reason: |-
        This annotation is derived from phylogenetic inference. In C.
        elegans, stress granules and P-bodies colocalize and share components
        (PMID:24367695), but the primary characterized roles of CAR-1 are in
        P-body/P-granule function, cytokinesis, and apoptosis regulation rather
        than stress response. Falcon deep research likewise frames CAR-1 as a
        regulated condensate component whose condensation increases under stress
        rather than as a dedicated stress-granule assembly factor.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            multiple condensate types (P-bodies, germ granules, stress granules) can coexist and interact
          reference_section_type: RESULTS
  - term:
      id: GO:0003723
      label: RNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation is consistent with experimental evidence. CAR-1 
        contains Sm domain and RGG box that bind RNA. The more specific mRNA 
        binding (GO:0003729) annotation exists via IBA.
      action: ACCEPT
      reason: IEA annotation is valid and supported by experimental evidence 
        demonstrating CAR-1 RNA binding via its Sm domain and RGG box 
        (PMID:16247027). The annotation is appropriately general as a parent 
        term to mRNA binding.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: UniProt annotation indicates nuclear localization based on 
        PMID:18430416, which identified CAR-1 as a transcriptional regulator 
        that binds the cdc-48.1 promoter. However, the predominant localization 
        of CAR-1 in other studies is cytoplasmic (P-bodies and P-granules).
      action: KEEP_AS_NON_CORE
      reason: Nuclear localization appears to be a minor or context-specific 
        aspect of CAR-1 function. The primary and well-characterized 
        localizations are to cytoplasmic P-bodies and P-granules. The 
        transcriptional regulator function in PMID:18430416 is atypical compared
        to other CAR-1 studies.
  - term:
      id: GO:0005681
      label: spliceosomal complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: This annotation is based on UniProt keyword mapping. While CAR-1 
        contains an Sm domain related to spliceosomal Sm proteins, CAR-1 itself 
        has an atypical Sm domain and functions in P-body/mRNA metabolism rather
        than splicing.
      action: REMOVE
      reason: This annotation is misleading. CAR-1 contains an atypical Sm 
        domain that is distinct from canonical spliceosomal Sm domains 
        (PMID:16247027). CAR-1 functions in mRNA metabolism and cytokinesis, not
        pre-mRNA splicing. The sequence divergence within the Sm domain is 
        predicted to confer unique RNA binding properties to this protein family
        distinct from spliceosomal Sm proteins.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Cytoplasmic localization is well-supported by multiple 
        experimental studies. CAR-1 localizes to cytoplasmic P-bodies and 
        P-granules.
      action: ACCEPT
      reason: IEA annotation is correct and redundant with multiple IDA 
        annotations for cytoplasm localization (PMID:16221731, PMID:16267265). 
        CAR-1 is a cytoplasmic protein that localizes to RNP granules.
  - term:
      id: GO:0006351
      label: DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: This annotation is based on UniProt keyword mapping from the 
        transcription regulator function described in PMID:18430416. However, 
        CAR-1's primary characterized function is post-transcriptional mRNA 
        regulation.
      action: KEEP_AS_NON_CORE
      reason: While PMID:18430416 provides evidence for CAR-1 involvement in 
        transcriptional regulation of cdc-48.1, this appears to be a secondary 
        or specialized function. The preponderance of evidence supports CAR-1's 
        primary role in post-transcriptional regulation through P-body/P-granule
        function.
  - term:
      id: GO:0006397
      label: mRNA processing
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: CAR-1 functions in mRNA metabolism through P-bodies, which are 
        sites of mRNA storage and degradation. CAR-1 colocalizes with DCAP-1, 
        the decapping enzyme.
      action: ACCEPT
      reason: |-
        IEA annotation is appropriate. CAR-1 is involved in
        post-transcriptional mRNA regulation as a P-body component. It functions
        with CGH-1 to regulate maternally loaded mRNAs required for cytokinesis
        (PMID:16247027). Falcon deep research describes CAR-1 as acting with
        CGH-1/DDX6 and interfacing with the mRNA decapping machinery (DCAP-1/DCAP-2),
        with context-dependent roles in either repressing translation or routing
        mRNAs into decay.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            Acts with **CGH-1/DDX6** and can interface with **mRNA decapping machinery**
          reference_section_type: RESULTS
  - term:
      id: GO:0008380
      label: RNA splicing
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: This annotation is based on UniProt keyword mapping, likely from 
        the Sm domain. However, CAR-1 has an atypical Sm domain and functions in
        mRNA metabolism, not pre-mRNA splicing.
      action: REMOVE
      reason: This annotation is incorrect. CAR-1's atypical Sm domain is 
        functionally distinct from canonical spliceosomal Sm proteins. CAR-1 
        functions in P-body-mediated mRNA regulation and cytokinesis, not RNA 
        splicing. There is no experimental evidence supporting CAR-1 involvement
        in splicing.
  - term:
      id: GO:0035770
      label: ribonucleoprotein granule
    evidence_type: IDA
    original_reference_id: PMID:25261697
    review:
      summary: CAR-1 is a component of OMA ribonucleoprotein particles that 
        regulate translation during oogenesis. CAR-1 was identified as an 
        OMA-1-associated protein in affinity purification experiments.
      action: ACCEPT
      reason: |-
        IDA annotation is well-supported. CAR-1 localizes to multiple
        types of RNP granules including P-bodies, P-granules, and OMA RNPs. This
        annotation captures the general RNP granule localization. Falcon deep
        research frames CAR-1 as a protein that partitions into cytoplasmic
        ribonucleoprotein condensates including germ granules and P-body-like foci.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      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.
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            CAR-1 localizes both to **P granules (germ granules)** and to **DCAP-1-positive cytoplasmic foci** interpreted as P-body-like structures.
          reference_section_type: RESULTS
  - term:
      id: GO:0000979
      label: RNA polymerase II core promoter sequence-specific DNA binding
    evidence_type: IDA
    original_reference_id: PMID:18430416
    review:
      summary: PMID:18430416 identified CAR-1 as binding to Element B in the 
        cdc-48.1 promoter using South-Western blotting from embryonic nuclear 
        extracts. However, this is an unusual function for CAR-1 compared to its
        well-characterized cytoplasmic RNA metabolism functions.
      action: UNDECIDED
      reason: The annotation is based on South-Western blotting which identifies
        proteins that bind DNA, but this method may not distinguish direct from 
        indirect binding. This finding has not been replicated and is 
        inconsistent with CAR-1's primary characterization as a cytoplasmic 
        RNA-binding protein. Further evidence would be needed to confirm this 
        atypical function.
      supported_by:
        - reference_id: PMID:18430416
          supporting_text: 2008 Mar 13. Involvement of HMG-12 and CAR-1 in the 
            cdc-48.1 expression of Caenorhabditis elegans.
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IMP
    original_reference_id: PMID:18430416
    review:
      summary: car-1(RNAi) reduces cdc-48.1 expression, supporting a positive 
        regulatory role. However, this may be indirect through mRNA 
        stabilization rather than transcriptional activation.
      action: KEEP_AS_NON_CORE
      reason: The annotation reflects a phenotypic observation. Given CAR-1's 
        primary role in mRNA metabolism, the effect on gene expression may be at
        the post-transcriptional level (mRNA stability/translation) rather than 
        transcriptional activation. The term is broad enough to encompass both 
        possibilities.
      supported_by:
        - reference_id: PMID:18430416
          supporting_text: 2008 Mar 13. Involvement of HMG-12 and CAR-1 in the 
            cdc-48.1 expression of Caenorhabditis elegans.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: PMID:16267265 reports CAR-1 affects ER organization, but the 
        primary localization data in this paper focuses on P-bodies, P-granules,
        spindle, and pericentriolar material. ER localization may be indirect or
        context-specific.
      action: KEEP_AS_NON_CORE
      reason: |-
        The paper describes organization of the endoplasmic reticulum is
        aberrant upon CAR-1 depletion, suggesting CAR-1 affects ER organization.
        However, ER localization is not a primary characterized site for CAR-1.
        The relationship may be functional rather than direct localization.
        Falcon deep research reinforces that CAR-1 is functionally coupled to the
        ER in embryos, with depletion disrupting ER reticulation and
        spindle/midzone-associated ER, consistent with an ER-linked mRNP/granule
        function rather than a constitutive ER residency.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            CAR-1 is also functionally coupled to the **endoplasmic reticulum (ER)** in embryos, where depletion disrupts ER reticulation and spindle/midzone-associated ER
          reference_section_type: RESULTS
  - term:
      id: GO:0072686
      label: mitotic spindle
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: CAR-1 is required for proper anaphase spindle structure. CAR-1 
        depletion causes failure of interzonal microtubule bundle formation. The
        localization to spindle may be related to CAR-1's function in regulating
        mRNAs required for spindle assembly.
      action: ACCEPT
      reason: IDA annotation is supported by functional evidence. CAR-1 
        depletion causes a specific defect in the microtubule cytoskeleton with 
        loss of interzonal microtubule bundles (PMID:16247027). This suggests 
        CAR-1 localizes to or functions at the spindle during cytokinesis.
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
  - term:
      id: GO:1990023
      label: mitotic spindle midzone
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: CAR-1 is required for spindle midzone formation. In car-1 
        depleted embryos, the spindle midzone fails to form, even though midzone
        components are present (PMID:16267265).
      action: ACCEPT
      reason: IDA annotation is well-supported. CAR-1 depletion causes failure 
        of interzonal microtubule bundle formation and loss of AIR-2 and ZEN-4 
        recruitment to the midzone (PMID:16247027). CAR-1 function is essential 
        for midzone assembly.
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25261697
    review:
      summary: CAR-1 interacts with OMA-1 in the context of OMA 
        ribonucleoprotein particles. CAR-1 also forms complexes with CGH-1 and 
        CEY-2 (PMID:16247027).
      action: REMOVE
      reason: |-
        Generic protein binding is uninformative here. The IPI records a
        protein-protein interaction (CAR-1 co-purified with OMA-1), but this
        OMA-1 interaction maps to no specific informative MF term. GO:0003729
        (mRNA binding) is an RNA-binding molecular function unrelated to this
        protein-protein interaction and is already separately annotated (IBA),
        so it is not a valid replacement. CAR-1's RNP-complex context is already
        captured by GO:1990904 (ribonucleoprotein complex, IDA, PMID:16247027).
      additional_reference_ids:
        - PMID:16247027
        - file:worm/car-1/car-1-deep-research-falcon.md
      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.
        - reference_id: PMID:16247027
          supporting_text: A complex containing the Sm protein CAR-1 and the RNA
            helicase CGH-1 is required for embryonic cytokinesis in 
            Caenorhabditis elegans.
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            Acts with **CGH-1/DDX6** and can interface with **mRNA decapping machinery**
          reference_section_type: RESULTS
  - term:
      id: GO:0000932
      label: P-body
    evidence_type: IDA
    original_reference_id: PMID:24367695
    review:
      summary: CAR-1 colocalizes with P-body components CGH-1 and PAB-1 in both 
        P-granules and P-bodies in embryos and gonads (PMID:24367695).
      action: ACCEPT
      reason: IDA annotation is well-supported by colocalization studies showing
        CAR-1 with P-body markers in multiple contexts.
      supported_by:
        - reference_id: PMID:24367695
          supporting_text: eCollection 2013. PAB-1, a Caenorhabditis elegans 
            poly(A)-binding protein, regulates mRNA metabolism in germline by 
            interacting with CGH-1 and CAR-1.
  - term:
      id: GO:0043186
      label: P granule
    evidence_type: IDA
    original_reference_id: PMID:24367695
    review:
      summary: CAR-1 localizes to P granules, the germline-specific RNP 
        particles in C. elegans. P-granule localization is well-documented 
        across multiple studies.
      action: ACCEPT
      reason: IDA annotation is well-supported by multiple studies. CAR-1 
        localizes to P-granules (germ-line specific ribonucleoprotein particles)
        (PMID:16267265) and colocalizes with PGL-1, a P-granule marker.
      supported_by:
        - reference_id: PMID:24367695
          supporting_text: eCollection 2013. PAB-1, a Caenorhabditis elegans 
            poly(A)-binding protein, regulates mRNA metabolism in germline by 
            interacting with CGH-1 and CAR-1.
  - term:
      id: GO:1990904
      label: ribonucleoprotein complex
    evidence_type: IDA
    original_reference_id: PMID:16247027
    review:
      summary: CAR-1 is part of a multiprotein RNP complex containing CGH-1 and 
        CEY-2. The interaction with CGH-1 is RNA-dependent.
      action: ACCEPT
      reason: |-
        IDA annotation is well-supported. CAR-1 is a component of a
        multiprotein complex that also contains the DEAD box RNA helicase,
        CGH-1, and a Y-box-containing protein, CEY-2 (PMID:16247027). Falcon deep
        research further describes CAR-1/CGH-1/IFET-1 repressive complexes that
        can repress translation and prevent decapping/decay in some developmental
        contexts.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:16247027
          supporting_text: A complex containing the Sm protein CAR-1 and the RNA
            helicase CGH-1 is required for embryonic cytokinesis in 
            Caenorhabditis elegans.
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            CAR-1/CGH-1/IFET-1 complexes can repress translation and prevent decapping/decay
          reference_section_type: RESULTS
  - term:
      id: GO:0000932
      label: P-body
    evidence_type: IDA
    original_reference_id: PMID:18515547
    review:
      summary: CAR-1 colocalizes with LARP-1 in germline P-bodies. This study 
        provides additional evidence for CAR-1 P-body localization.
      action: ACCEPT
      reason: IDA annotation is supported. LARP-1 colocalizes with P bodies and 
        CAR-1 is established as a P-body component.
      supported_by:
        - reference_id: PMID:18515547
          supporting_text: C. elegans La-related protein, LARP-1, localizes to 
            germline P bodies and attenuates Ras-MAPK signaling during 
            oogenesis.
  - term:
      id: GO:0000242
      label: pericentriolar material
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: CAR-1 localizes to pericentriolar material as shown in 
        PMID:16267265. This localization is consistent with CAR-1's role in 
        spindle-related processes during cytokinesis.
      action: ACCEPT
      reason: IDA annotation captures a specific localization relevant to 
        CAR-1's function in cytokinesis and spindle organization.
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
  - term:
      id: GO:0000932
      label: P-body
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: Original characterization of CAR-1 P-body localization. CAR-1 
        colocalizes with DCAP-1, the mRNA decapping component, in cytoplasmic 
        foci.
      action: ACCEPT
      reason: IDA annotation from the foundational CAR-1 characterization paper.
        This study established CAR-1 as a P-body component.
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:16221731
    review:
      summary: CAR-1 localizes to cytoplasmic particles in the gonad and early 
        embryo.
      action: ACCEPT
      reason: IDA annotation is well-supported. CAR-1 is primarily a cytoplasmic
        protein that localizes to various RNP granules.
      supported_by:
        - reference_id: PMID:16221731
          supporting_text: A conserved RNA-protein complex component involved in
            physiological germline apoptosis regulation in C.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: CAR-1 localizes to cytoplasmic foci and P-granules.
      action: ACCEPT
      reason: IDA annotation is correct. CAR-1 is a cytoplasmic protein.
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
  - term:
      id: GO:0043186
      label: P granule
    evidence_type: IDA
    original_reference_id: PMID:16221731
    review:
      summary: CAR-1 localizes to P granules and associates with CGH-1 in a 
        conserved germline RNP complex.
      action: ACCEPT
      reason: IDA annotation is well-supported. P-granule localization is a core
        aspect of CAR-1 function in the germline.
      supported_by:
        - reference_id: PMID:16221731
          supporting_text: A conserved RNA-protein complex component involved in
            physiological germline apoptosis regulation in C.
  - term:
      id: GO:0043186
      label: P granule
    evidence_type: IDA
    original_reference_id: PMID:16247027
    review:
      summary: CAR-1 localizes to P-granules that concentrate in germline 
        precursors. P-granule localization is confirmed by colocalization with 
        PGL-1.
      action: ACCEPT
      reason: IDA annotation is well-supported. CAR-1 localizes to 
        RNA-containing P-granules that concentrate in the germline precursors 
        (PMID:16247027).
      supported_by:
        - reference_id: PMID:16247027
          supporting_text: A complex containing the Sm protein CAR-1 and the RNA
            helicase CGH-1 is required for embryonic cytokinesis in 
            Caenorhabditis elegans.
  - term:
      id: GO:0043186
      label: P granule
    evidence_type: IDA
    original_reference_id: PMID:16267265
    review:
      summary: Original characterization showing CAR-1 localization to 
        P-granules.
      action: ACCEPT
      reason: IDA annotation from foundational CAR-1 paper. P-granule 
        localization is central to CAR-1 germline function.
      supported_by:
        - reference_id: PMID:16267265
          supporting_text: Nov 2. CAR-1, a protein that localizes with the mRNA 
            decapping component DCAP-1, is required for cytokinesis and ER 
            organization in Caenorhabditis elegans embryos.
  - term:
      id: GO:0000281
      label: mitotic cytokinesis
    evidence_type: IMP
    original_reference_id: PMID:16247027
    review:
      summary: CAR-1 is essential for embryonic cytokinesis. car-1(RNAi) and 
        car-1 mutant embryos fail to complete cytokinesis, with cleavage furrows
        regressing and spindle midzone failing to form.
      action: NEW
      reason: |-
        This is a core function of CAR-1 not explicitly annotated. CAR-1
        was named for Cytokinesis, Apoptosis, RNA-associated reflecting its
        essential role in cytokinesis. Multiple studies demonstrate cytokinesis
        failure upon CAR-1 depletion. Falcon deep research confirms CAR-1 is
        required for late cytokinesis/scission, with depletion causing cleavage
        furrows to ingress then regress alongside disrupted membrane accumulation
        and spindle midzone organization.
      additional_reference_ids:
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:16247027
          supporting_text: A complex containing the Sm protein CAR-1 and the RNA
            helicase CGH-1 is required for embryonic cytokinesis in 
            Caenorhabditis elegans.
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            CAR-1 is required for late cytokinesis/scission; depletion causes cleavage furrows to ingress then regress and disrupts membrane accumulation and spindle midzone organization
          reference_section_type: RESULTS
  - term:
      id: GO:0017148
      label: negative regulation of translation
    evidence_type: IMP
    original_reference_id: PMID:18695046
    review:
      summary: CAR-1 functions in translational repression as part of P-body and
        OMA RNP complexes. CAR-1 is part of the IFET-1/CGH-1/CAR-1/PATR-1
        repressive complex.
      action: NEW
      reason: |-
        This is a core molecular function of CAR-1, demonstrated by direct
        mutant/RNAi phenotype evidence. Noble et al. 2008 (PMID:18695046) show
        that loss of CAR-1 causes ectopic GLP-1 (Notch receptor) protein
        expression in oocytes while glp-1 mRNA levels remain unchanged,
        establishing that CAR-1 controls glp-1 translation rather than mRNA
        production or stability. This is consistent with CAR-1 acting in
        PUF-dependent translational repression and with its association with
        translational repressors in OMA RNPs (PMID:25261697). The original IBA
        annotation (GO_REF:0000033) is retained as a supporting reference.
      additional_reference_ids:
        - GO_REF:0000033
        - file:worm/car-1/car-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:18695046
          supporting_text: |-
            ectopic GLP-1 protein expression in oocytes of both wild-type and fog-2(q71) arrested gonads
          reference_section_type: RESULTS
        - reference_id: PMID:18695046
          supporting_text: |-
            glp-1 mRNA levels were similar in car-1(tm1753) mutant and wild-type animals, which supports CAR-1 control of glp-1 translation rather than mRNA production or stability
          reference_section_type: RESULTS
        - reference_id: file:worm/car-1/car-1-deep-research-falcon.md
          supporting_text: |-
            In the germline/oogenesis, CAR-1 promotes PUF-dependent repression of the Notch-like receptor mRNA **glp-1**, and car-1 depletion elevates GLP-1 protein while glp-1 mRNA levels remain similar, consistent with primary control at the translation level.
          reference_section_type: RESULTS
  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:16221731
    review:
      summary: CAR-1 regulates physiological germline apoptosis. car-1(RNAi) 
        leads to increased germline cell death, indicating CAR-1 normally 
        suppresses apoptosis.
      action: NEW
      reason: This is a core function of CAR-1 (the A in CAR-1 stands for 
        Apoptosis). Depletion of CAR-1 increases physiological germline 
        apoptosis, demonstrating a negative regulatory role.
      supported_by:
        - reference_id: PMID:16221731
          supporting_text: A conserved RNA-protein complex component involved in
            physiological germline apoptosis regulation in C.
references:
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings:
      - statement: CAR-1 is orthologous to LSM14 family proteins 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: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:16221731
    title: A conserved RNA-protein complex component involved in physiological 
      germline apoptosis regulation in C. elegans.
    findings:
      - statement: CAR-1 associates with CGH-1 and Y-box proteins in a conserved
          germline RNP complex
      - statement: The CGH-1/CAR-1 interaction is conserved in Drosophila 
          oocytes
      - statement: car-1(RNAi) increases physiological germline apoptosis
      - statement: CAR-1 is critical for oogenesis
  - 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: CAR-1 contains an atypical Sm domain and RGG box that bind 
          RNA
      - statement: CAR-1 forms an RNA-dependent complex with CGH-1 and CEY-2
      - statement: CAR-1 localizes to P-granules and smaller cytoplasmic 
          particles
      - statement: The Sm domain is essential for CAR-1 function but not 
          localization
      - statement: CAR-1 depletion causes failure of interzonal microtubule 
          bundle formation
      - statement: CAR-1 depletion prevents AIR-2 and ZEN-4 targeting to spindle
          midzone
      - statement: CGH-1 controls CAR-1 particle localization
  - id: PMID:16267265
    title: CAR-1, a protein that localizes with the mRNA decapping component 
      DCAP-1, is required for cytokinesis and ER organization in Caenorhabditis 
      elegans embryos.
    findings:
      - statement: CAR-1 colocalizes with DCAP-1 in P-bodies
      - statement: CAR-1 localizes to P-granules
      - statement: car-1 inhibition causes late cytokinesis failures
      - statement: Spindle midzone fails to form in car-1 depleted embryos
      - statement: ER organization is disrupted in car-1 depleted embryos
  - id: PMID:18430416
    title: Involvement of HMG-12 and CAR-1 in the cdc-48.1 expression of 
      Caenorhabditis elegans.
    findings:
      - statement: CAR-1 was identified as binding to Element B in cdc-48.1 
          promoter
      - statement: car-1(RNAi) decreases cdc-48.1 and cdc-48.2 expression in 
          embryos
  - id: PMID:18515547
    title: C. elegans La-related protein, LARP-1, localizes to germline P bodies
      and attenuates Ras-MAPK signaling during oogenesis.
    findings:
      - statement: LARP-1 colocalizes with P bodies containing CAR-1
  - id: PMID:18695046
    title: Maternal mRNAs are regulated by diverse P body-related mRNP granules
      during early Caenorhabditis elegans development.
    findings:
      - statement: Loss of CAR-1 causes ectopic GLP-1 protein expression in
          oocytes while glp-1 mRNA levels remain unchanged, indicating CAR-1
          controls glp-1 translation rather than mRNA production or stability
        supporting_text: |-
          glp-1 mRNA levels were similar in car-1(tm1753) mutant and wild-type animals, which supports CAR-1 control of glp-1 translation rather than mRNA production or stability
      - statement: CAR-1 promotes PUF-dependent translational repression of glp-1
          during late oogenesis
  - 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 CAR-1 in P-granules and P-bodies
      - statement: PAB-1, CGH-1, and CAR-1 interact in mRNA metabolism 
          regulation
      - statement: CGH-1 controls CAR-1 localization; CAR-1 does not control 
          CGH-1 localization
      - statement: PAB-1 affects CGH-1 and CAR-1 localization
  - id: PMID:25261697
    title: Translational control of the oogenic program by components of OMA 
      ribonucleoprotein particles in Caenorhabditis elegans.
    findings:
      - statement: CAR-1 is a component of OMA-1 ribonucleoprotein particles
      - statement: OMA RNPs contain translational repressors and activators
  - id: file:worm/car-1/car-1-deep-research-falcon.md
    title: Falcon (Edison Scientific) deep research report on C. elegans car-1 (Q9XW17)
    findings:
      - statement: |-
          CAR-1 is a conserved LSM14/Scd6/Rap55-family RNA-binding protein that
          partitions into cytoplasmic RNP condensates (P-bodies/P-body-like foci
          and germ granules) and acts as an adaptor/scaffold rather than an enzyme.
        supporting_text: |-
          CAR-1 is not an enzyme; it is best annotated as an **RNA-binding mRNP assembly/adaptor protein**
        reference_section_type: RESULTS
      - statement: |-
          CAR-1 directly binds RNA, with its RGG region binding poly(U) in vitro
          and an N-terminal Lsm domain consistent with the LSM14/Scd6/Rap55 family.
        supporting_text: |-
          RGG region binds poly(U) in vitro, supporting direct RNA-binding capacity.
        reference_section_type: RESULTS
      - statement: |-
          CAR-1 promotes translational repression of specific maternal mRNAs,
          including PUF-dependent repression of glp-1 in oogenesis.
        supporting_text: |-
          In the germline/oogenesis, CAR-1 promotes PUF-dependent repression of the Notch-like receptor mRNA **glp-1**, and car-1 depletion elevates GLP-1 protein while glp-1 mRNA levels remain similar, consistent with primary control at the translation level.
        reference_section_type: RESULTS
      - statement: |-
          CAR-1 is required for late embryonic cytokinesis and ER organization;
          depletion causes furrow regression and disrupted spindle midzone.
        supporting_text: |-
          CAR-1 is required for late cytokinesis/scission; depletion causes cleavage furrows to ingress then regress and disrupts membrane accumulation and spindle midzone organization
        reference_section_type: RESULTS
      - statement: |-
          In neurons, CAR-1/LSM14 represses micu-1 to modulate mitochondrial Ca2+
          dynamics and acts as a cell-intrinsic inhibitor of PLM axon regrowth.
        supporting_text: |-
          represses neuronal **micu-1**, thereby modulating mitochondrial Ca2+ uptake dynamics after axotomy and acting as a cell-intrinsic inhibitor of PLM axon regrowth.
        reference_section_type: RESULTS
      - statement: |-
          CAR-1 contributes a scaffold role to decapping condensates; in
          edc-3(0);edc-4(0) embryos car-1 RNAi reduces DCAP-2 foci 2-4.5-fold.
        supporting_text: |-
          car-1 RNAi (64% knockdown) in this background reduces DCAP-2 foci 2–4.5-fold, supporting a scaffold role for CAR-1 in alternative condensate frameworks when canonical scaffolds are absent.
        reference_section_type: RESULTS
      - statement: |-
          CAR-1 organizes condensate-condensate interactions supporting
          piRNA-dependent transgenerational silencing, promoting CGH-1 perinuclear
          localization and its binding to PRG-1/WAGO-1.
        supporting_text: |-
          CAR-1 promotes CGH-1 perinuclear localization/condensate formation, and CAR-1 depletion reduces CGH-1 binding to PRG-1 and WAGO-1
        reference_section_type: RESULTS
core_functions:
  - description: CAR-1 is an mRNA-binding protein that functions in 
      post-transcriptional regulation of maternally loaded mRNAs. It directly 
      binds RNA through its atypical Sm domain and RGG box. CAR-1 forms an 
      RNA-dependent complex with CGH-1 (DDX6 homolog) and CEY-2, functioning in 
      P-body and P-granule mediated mRNA regulation. It is essential for 
      embryonic cytokinesis and regulates physiological germline apoptosis.
    molecular_function:
      id: GO:0003729
      label: mRNA binding
    directly_involved_in:
      - id: GO:0000281
        label: mitotic cytokinesis
      - id: GO:0043066
        label: negative regulation of apoptotic process
      - id: GO:0017148
        label: negative regulation of translation
    locations:
      - id: GO:0043186
        label: P granule
      - id: GO:0000932
        label: P-body
    in_complex:
      id: GO:1990904
      label: ribonucleoprotein complex
proposed_new_terms: []
suggested_questions:
  - question: Is CAR-1's role in transcriptional regulation of cdc-48.1 
      (PMID:18430416) a true transcriptional function or an indirect effect 
      through mRNA regulation?
  - question: What specific mRNAs does CAR-1 regulate to control cytokinesis and
      anaphase spindle structure?
  - question: Does CAR-1 play a direct role in piRNA silencing pathways as 
      suggested by some studies of CAR-1/CGH-1 function?
suggested_experiments:
  - description: CLIP-seq or RIP-seq to identify direct CAR-1 mRNA targets in 
      embryos and germline.
  - description: Determine whether CAR-1's effect on cdc-48.1 expression is at 
      the transcriptional or post-transcriptional level.
  - description: Characterize the specific mRNAs regulated by CAR-1 that are 
      required for interzonal microtubule bundle formation.
tags:
  - caeel-p-granules

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Tags

Deep Research

Falcon

Research Report: Functional Annotation of C. elegans car-1 (UniProt Q9XW17; ORF Y18D10A.17)

Executive summary

Gene/protein identity verification (mandatory)

1) Key concepts and definitions (current understanding)

1.1 LSM14/Scd6/Rap55 proteins (CAR-1)

1.2 Processing bodies (P-bodies) and germ granules

1.3 Condensate “specialization” and inter-condensate coupling

2) Functional annotation: molecular function, localization, and pathways

2.1 Molecular function (what CAR-1 does)

2.2 Subcellular localization (where CAR-1 acts)

2.3 Biological processes and pathways

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2023: condensate cooperativity in transgenerational gene silencing

3.2 2024: embryonic mRNA clearance and P-body specialization (EDC-3/EDC-4)

3.3 2024: oogenesis—ER morphology, phase transitions, and translational repression

4) Current applications and real-world implementations

4.1 CAR-1 as an experimental handle for mRNP granule biology in vivo

4.2 Translational relevance via conserved LSM14-family biology

5) Expert opinions and analysis

6) Quantitative statistics and data highlights

Evidence summary table

Notes on limitations

Key primary sources (URLs + publication dates)

Artifacts

Citations

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