FCA is a nuclear RNA-binding regulator with two RNA recognition motifs and a WW protein-interaction domain. It promotes flowering in Arabidopsis by limiting expression of the floral repressor FLC. FCA binds COOLAIR antisense RNAs and helps couple RNA processing to chromatin regulation, including association with the PRC2 subunit CLF. Its interaction with the CPSF component FY controls proximal polyadenylation, including autoregulatory processing of FCA pre-mRNA. FCA forms dynamic nuclear bodies whose assembly is promoted by FLL2. FCA and FPA have overlapping requirements in reproductive development but distinct molecular interactions. FCA is not an abscisic-acid receptor.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | TAS PMID:17916737 Widespread role for the flowering-time regulators FCA and FP... | ACCEPT | Summary: FCA is recruited to FLC chromatin co-transcriptionally via binding to nascent COOLAIR, and ChIP shows FCA enrichment at FLC that depends on COOLAIR. Reason: Chromatin association of FCA at its key target is supported experimentally (Tian et al. 2019 ChIP; reduced FCA enrichment when COOLAIR function is lost). The original TAS statement from Baurle et al. 2007 is consistent with these later data. Accepted as a location of the co-transcriptional RNA-processing activity. Supporting Evidence: PMID:31032401 Loss of COOLAIR function results in a reduction in FCA and CLF enrichment, which, in turn, decreases H3K27me3 levels at FLC. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: Generic nucleic acid binding inferred from the RRM superfamily InterPro signature. Reason: Correct but uninformative. FCA is an RRM-containing RNA-binding protein; the more specific RNA binding (GO:0003723) is directly supported. Proposed replacements: RNA binding Supporting Evidence: PMID:9182761 FCA has been cloned and shown to encode a protein containing two RNA-binding domains and a WW protein interaction domain. |
| GO:0003723 RNA binding | IDA PMID:9182761 FCA, a gene controlling flowering time in Arabidopsis, encod... | ACCEPT | Summary: FCA was identified as an RRM-containing protein; later work established it as a nuclear RNA-binding protein that binds its own pre-mRNA and COOLAIR. Reason: RNA binding is the core molecular activity of FCA. The cached 1997 abstract only describes the RRM domains, but the IDA was made by curators from the full text, and RNA binding has since been confirmed (FCA binds nascent COOLAIR transcripts; Tian et al. 2019). Supporting Evidence: PMID:9182761 FCA has been cloned and shown to encode a protein containing two RNA-binding domains and a WW protein interaction domain. PMID:12805228 We show that FCA is a nuclear RNA-binding protein and that its WW domain is required for this autoregulation. |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: RNA binding inferred from RRM domain (InterPro IPR000504). Reason: Consistent with experimental evidence that FCA is an RNA-binding protein. Supporting Evidence: PMID:12805228 We show that FCA is a nuclear RNA-binding protein and that its WW domain is required for this autoregulation. |
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: mRNA binding is an inherited RRM-protein capability compatible with FCA-mediated pre-mRNA processing. Reason: The inspected PTN000609546 IBD supports inherited mRNA binding. Native FCA regulates its own pre-mRNA and other RNA processing; that processing phenotype alone is not a direct binding assay for each mRNA substrate. Together with experimentally established FCA RNA binding, the ancestral inference is biologically defensible without asserting measured affinity for FCA mRNA. Supporting Evidence: PMID:12805228 We demonstrate here that FCA negatively regulates its own expression by ultimately promoting cleavage and polyadenylation within intron 3. file:genes/ARATH/FCA/FCA-bioinformatics/README.md |
| GO:0005515 protein binding | IPI PMID:31032401 PRC2 recruitment and H3K27me3 deposition at FLC require FCA ... | REMOVE | Summary: FCA physically interacts with SSU72 through RRM1. Reason: The SSU72 interaction is supported, but bare protein binding is removed under the protein-binding policy; this does not reject the interaction. Supporting Evidence: PMID:31032401 SSU72 interacts with the RRM1 motif of FCA to antagonize the binding of FCA and COOLAIR. |
| GO:0005515 protein binding | IPI PMID:31043738 Arabidopsis FLL2 promotes liquid-liquid phase separation of ... | REMOVE | Summary: FCA interacts with FLL1 and FLL3 in yeast two-hybrid assays. Reason: The exact FLL1/FLL3 interactions are supported in Extended Data Fig.5d. FLL2 has distinct phase-separation/crosslinking evidence and is not substituted for these partners. Remove only the uninformative protein-binding term. Supporting Evidence: PMID:31043738 using yeast two-hybrid assays, we found that FLL1 and FLL3 interacted with FCA, while FLL2 did not |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization propagated by PAINT. Reason: FCA is experimentally a nuclear protein. Supporting Evidence: PMID:12805228 Consistent with this possibility and the fact that pre-mRNA processing is a nuclear event, we found that FCA is localized to the nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization from UniProt subcellular location mapping. Reason: Consistent with experimental data. Supporting Evidence: PMID:12805228 Consistent with this possibility and the fact that pre-mRNA processing is a nuclear event, we found that FCA is localized to the nucleus. |
| GO:0005634 nucleus | ISM GO_REF:0000122 | ACCEPT | Summary: Nuclear localization predicted by AtSubP. Reason: Consistent with experimental data. Supporting Evidence: PMID:12805228 Consistent with this possibility and the fact that pre-mRNA processing is a nuclear event, we found that FCA is localized to the nucleus. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | UNDECIDED | Summary: A cytoplasmic FCA pool is not resolved by predominantly nuclear reporter localization. Reason: The onion-cell FCA:GUS assay in PMID:12805228 establishes predominant nuclear localization, not exclusion from cytoplasm. Native nuclear bodies and chromatin association likewise do not exclude a minor or transient cytoplasmic pool. The PTN000609546 cytoplasm IBD was verified; its target-specific inheritance remains unresolved, with no demonstrated loss or tree-placement error. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000609546 UNRESOLVED Actual cytoplasm IBD inspected; nuclear predominance is not evidence of loss of the inferred cytoplasmic localization. Supporting Evidence: PMID:12805228 In contrast, cells transfected with FCA:GUS showed GUS activity predominantly in the nucleus indicating that FCA is a nuclear-localized protein (Figure 5 A and B). file:genes/ARATH/FCA/FCA-bioinformatics/README.md |
| GO:0005737 cytoplasm | ISM GO_REF:0000122 | UNDECIDED | Summary: A cytoplasmic FCA pool is not resolved by predominantly nuclear reporter localization. Reason: The onion-cell FCA:GUS assay in PMID:12805228 establishes predominant nuclear localization, not exclusion from cytoplasm. Native nuclear bodies and chromatin association likewise do not exclude a minor or transient cytoplasmic pool. The AtSubP sequence prediction has neither been independently confirmed nor contradicted by an exclusion assay. Supporting Evidence: PMID:12805228 In contrast, cells transfected with FCA:GUS showed GUS activity predominantly in the nucleus indicating that FCA is a nuclear-localized protein (Figure 5 A and B). |
| GO:0009553 embryo sac development | IGI PMID:17916737 Widespread role for the flowering-time regulators FCA and FP... | KEEP AS NON CORE | Summary: fca fpa double mutants show defects in female gametophyte development (IGI). Reason: Genetic requirement shared redundantly with FPA, probably reflecting misregulated RNA 3'-processing/silencing at multiple targets; a pleiotropic, non-core role. Supporting Evidence: PMID:17916737 Female gametophytic development and early embryonic development are particularly susceptible to malfunctions in FCA and FPA. |
| GO:0009793 embryo development ending in seed dormancy | IGI PMID:17916737 Widespread role for the flowering-time regulators FCA and FP... | KEEP AS NON CORE | Summary: fca fpa double mutants show early embryo defects (IGI). Reason: Pleiotropic genetic requirement shared with FPA; not the core function of FCA. Supporting Evidence: PMID:17916737 Female gametophytic development and early embryonic development are particularly susceptible to malfunctions in FCA and FPA. |
| GO:0009909 regulation of flower development | IEA GO_REF:0000117 | ACCEPT | Summary: Regulation of flower development from ARBA machine learning. Reason: FCA promotes the floral transition through repression of FLC; the general regulation term is consistent with the IMP evidence. Supporting Evidence: PMID:9182761 A strong promoter of the transition to flowering in Arabidopsis is encoded by FCA. |
| GO:0009909 regulation of flower development | IMP PMID:11457959 Analysis of flowering time control in Arabidopsis by compari... | ACCEPT | Summary: fca mutants are late flowering; analysis in double/triple mutants places FCA in the autonomous pathway. Reason: Well-established genetic role of FCA as a promoter of flowering in the autonomous pathway. Supporting Evidence: PMID:11457959 These pathways are represented by the genes CO , FCA , and GA1 , which act in the long-day, autonomous, and gibberellin pathways, respectively. |
| GO:0010427 abscisic acid binding | IDA NOT PMID:19078995 FCA does not bind abscisic acid. | ACCEPT | Summary: NOT abscisic acid binding. Risk et al. showed that FCA does not bind ABA. Reason: The negative annotation is correct: the earlier claim that FCA is an ABA receptor was refuted (and the original paper retracted). Retaining the NOT annotation is valuable. Supporting Evidence: PMID:19078995 However, we find that FCA does not bind ABA, suggesting that the quality of the proteins assayed and the sensitivity of the ABA-binding assay have led Razem et al. to erroneous conclusions. |
| GO:0016604 nuclear body | IDA PMID:31043738 Arabidopsis FLL2 promotes liquid-liquid phase separation of ... | ACCEPT | Summary: FCA-eGFP localizes to liquid-like nuclear bodies (Fang et al. 2019). Reason: Direct imaging evidence; nuclear condensates are functionally linked to FCA-mediated proximal polyadenylation. Supporting Evidence: PMID:31043738 We thus conclude that FCA localizes to nuclear bodies with liquid-like properties, suggesting that FCA can undergo liquid-liquid phase separation in vivo. |
| GO:0031048 regulatory ncRNA-mediated heterochromatin formation | IMP PMID:17916737 Widespread role for the flowering-time regulators FCA and FP... | KEEP AS NON CORE | Summary: FCA supports locus-dependent RNA-mediated chromatin silencing beyond its flowering target. Reason: Retain the existing locus-dependent RNA-mediated silencing role as non-core. PMID:17916737 reports effects on asymmetric DNA methylation at some loci and methylation-independent effects at others. Later FPA AtSN1 read-through results cannot be generalized to refute FCA silencing at all loci. FCA binds COOLAIR and connects it with chromatin regulators; it is not itself a histone-modifying enzyme. Supporting Evidence: PMID:17916737 We show that they are required for RNA-mediated chromatin silencing of a range of loci in the genome. PMID:31043738 FCA promotes proximal polyadenylation of transcripts from many loci in the genome, previously classified as UAs4, as well as COOLAIR transcripts9. |
| GO:1990904 ribonucleoprotein complex | IBA GO_REF:0000033 | ACCEPT | Summary: FCA participates in RNA-containing assemblies through direct COOLAIR binding. Reason: GO:1990904 requires an RNA-protein complex, not poly(A)-binding activity or permanent CPSF membership. Direct in vivo and in vitro FCA-COOLAIR association supports the broad complex claim. The PTN002768817 IBD was inspected; its PABP seeds do not make the broad RNP term false for FCA. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002768817 SUPPORTS TRANSFER The ancestral RNP claim is independently supported by native FCA-COOLAIR assemblies; no PABP activity is inferred. Supporting Evidence: PMID:31032401 FCA physically binds COOLAIR in vitro and in vivo. file:genes/ARATH/FCA/FCA-bioinformatics/README.md |
| GO:0106222 lncRNA binding | IDA PMID:31032401 PRC2 recruitment and H3K27me3 deposition at FLC require FCA ... | NEW | Summary: NEW. FCA binds nascent COOLAIR antisense lncRNA at FLC, and this binding is antagonized by SSU72. Reason: More informative MF than generic RNA binding for the key target of FCA in flowering-time control; directly shown by RNA immunoprecipitation-type assays in Tian et al. 2019. Supporting Evidence: PMID:31032401 We report that the RNA binding protein FCA interacts with the PRC2 subunit CURLY LEAF (CLF) and binds nascent COOLAIR transcripts to allow deposition of H3K27me3 at FLC. |
| GO:0110104 mRNA alternative polyadenylation | IMP PMID:12805228 Autoregulation of FCA pre-mRNA processing controls Arabidops... | NEW | Summary: NEW. FCA promotes selection of a promoter-proximal poly(A) site within its own intron 3 (FCA-beta), and of proximal sites in COOLAIR and many other loci, via interaction with FY. Reason: FCA participates directly in poly(A) site choice: it binds the RNA and recruits the CPSF component FY to the proximal site (participation, not mere necessity). Directly demonstrated for FCA autoregulation and supported by genome-wide data. Supporting Evidence: PMID:12805228 We demonstrate here that FCA negatively regulates its own expression by ultimately promoting cleavage and polyadenylation within intron 3. PMID:12809608 FCA expression is autoregulated through the use of different polyadenylation sites within the FCA pre-mRNA, and the FCA/FY interaction is required for efficient selection of the promoter-proximal polyadenylation site. |
Loading supporting content…
Download this section (compressed HTML)Q: What RNA sequence or structural features does FCA recognise to select proximal poly(A) sites, and how is specificity for COOLAIR versus its own intron 3 achieved?
Q: How does FCA-mediated proximal termination physically hand over to the FLD/LD/SDG26 chromatin module (via FY-SDG26 contacts or via the CPF-like APRF1/LD phosphatase module)?
Experiment: Map FCA RNA-binding sites genome-wide by iCLIP or HyperTRIBE in wild type and RRM point mutants, and correlate with proximal poly(A) site usage measured by direct RNA sequencing.
Hypothesis: FCA binds specific motifs upstream of proximal poly(A) sites that it promotes.
Type: iCLIP / direct RNA sequencing
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)