MEX-5 is a tandem CCCH zinc-finger RNA-binding protein that works with MEX-6 to pattern maternal gene expression and soma/germline asymmetry in the early Caenorhabditis elegans embryo. It preferentially binds U-rich RNA, including AU-rich 3′-UTR elements. Its effects depend on the RNA target: MEX-5/6 promote zif-1 expression and repress maternal mom-2 translation. PAR-dependent phosphorylation and mobility changes generate an anterior-enriched cytoplasmic gradient; MEX-5 also binds Polo kinases and contributes to their asymmetric localization. By binding RNA, MEX-5 can dissolve reconstituted PGL-3/RNA condensates, providing a mechanism for spatial control of germ granules together with other embryonic factors. Tagged MEX-5 is also observed on granules in germline blastomeres.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IBA GO_REF:0000033 | ACCEPT | Summary: MEX-5 binds an AU-rich 3′-UTR substrate directly in purified-protein assays. Reason: The exact target inherits the positive PTN002648882 assertion and PMID:17264081 directly assays both paralogs against TNF-ARE. Preference for U-rich RNA with less discrimination than TTP is compatible with AU-rich region binding; the term does not require exclusive recognition of a canonical ARE. Supporting Evidence: file:worm/mex-5/mex-5-primary-evidence.md Both methods reveal that MEX-5 and MEX-6 bind to TNF-ARE RNA. file:worm/mex-5/mex-5-paint-lineage.md Both MEX-5 and MEX-6 descend from PTN002648882, which supplies the five source IBAs |
| GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening | IBA GO_REF:0000033 | ACCEPT | Summary: MEX-5 retains the phylogenetically inferred contribution to mRNA poly(A) tail shortening. Reason: Actual descent from positive IBD PTN002648882 is verified. MEX-5/6-dependent maternal RNA turnover and recruitment of P-body decay machinery are biologically consistent with the transfer. Tail hydrolysis is performed by deadenylases; an RNA-binding adaptor may participate without being catalytic. These target observations do not by themselves measure tail shortening, but no target-specific loss contradicts the ancestral process assertion. Supporting Evidence: file:worm/mex-5/mex-5-paint-lineage.md Both MEX-5 and MEX-6 descend from PTN002648882, which supplies the five source IBAs file:worm/mex-6/mex-6-deep-research-falcon.md In embryos depleted of MEX-5/6, LSM-1 is not recruited to P bodies and maternal mRNAs remain stabilized, indicating that MEX-5/6 promote maternal mRNA turnover in somatic blastomeres |
| GO:0000900 mRNA regulatory element binding translation repressor activity | IBA GO_REF:0000033 | ACCEPT | Summary: MEX-5 participates in repression of maternal mom-2 translation. Reason: The positive repressor IBD at PTN002648882 agrees with maternal Wnt 3′-UTR experiments. MEX-5 is directly tested in RNA binding, while combined MEX-5/6 depletion establishes the pair-level repression phenotype. MEX-6 retains inherited activity with that experimental scope. Relief of POS-1 repression on zif-1 is target-dependent positive regulation and does not negate repression of mom-2. Supporting Evidence: file:worm/mex-5/mex-5-primary-evidence.md The contrary is true for mom-2, where POS-1 promotes translation in P2 and MEX-5/6 represses translation in EMS. file:worm/mex-5/mex-5-paint-lineage.md Both MEX-5 and MEX-6 descend from PTN002648882, which supplies the five source IBAs |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: MEX-5 is a cytoplasmic protein that forms a concentration gradient enriched in the anterior of the early embryo. The cytosol annotation is consistent with experimental data showing cytoplasmic localization (PMID:10882103, PMID:18199581). Reason: Cytosol is an appropriate term for MEX-5. MEX-5 is asymmetrically localized in the cytoplasm with enrichment in the anterior. UniProt confirms cytoplasmic localization based on multiple publications. Supporting Evidence: PMID:10882103 MEX-5 is a novel, cytoplasmic protein that is localized through PAR activities to the anterior pole of the 1-cell stage embryo. PMID:18199581 These polo kinases are asymmetrically localized along the anteroposterior axis of newly fertilized C. elegans embryos in a pattern identical to that of MEX-5 and MEX-6. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5 is a non-enzymatic, cytoplasmic RNA-binding protein with **two CCCH zinc-finger domains** |
| GO:0160134 protein-RNA sequence-specific adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: MEX-5 retains inherited sequence-selective protein-RNA adaptor activity. Reason: The target descends from positive IBD PTN002648882. U-rich recognition is sequence preference even though many transcripts contain the motif and specificity is lower than TTP. The conserved RNA-binding module and protein interactions support adaptor function; lack of exclusive transcript recognition is not a biological refutation. Supporting Evidence: file:worm/mex-5/mex-5-primary-evidence.md Both methods reveal that MEX-5 and MEX-6 bind to TNF-ARE RNA. file:worm/mex-5/mex-5-paint-lineage.md Both MEX-5 and MEX-6 descend from PTN002648882, which supplies the five source IBAs PMID:18199581 We show that polo kinases, via their polo box domains, bind to and regulate the activity of two key polarity proteins, MEX-5 and MEX-6. |
| GO:0003677 DNA binding | IEA GO_REF:0000043 | UNDECIDED | Summary: The DNA-binding keyword transfer is unresolved. Reason: The source UniProt record carries a DNA-binding keyword, but the checked primary biochemistry establishes RNA recognition. RNA-binding CCCH fingers do not exclude DNA binding. No direct target DNA-binding or DNA-negative assay was established, so the previous categorical rejection is withdrawn pending clarification of the keyword basis. Supporting Evidence: file:worm/mex-5/mex-5-uniprot.txt DNA-binding; Metal-binding; |
| GO:0003723 RNA binding | IEA GO_REF:0000043 | ACCEPT | Summary: MEX-5 is well-established as an RNA-binding protein through its CCCH tandem zinc fingers. Experimental studies demonstrate high-affinity mRNA binding with Kd ~10 nM (PMID:17264081). Reason: RNA binding is a core function of MEX-5, extensively documented experimentally. MEX-5 binds mRNA with high affinity to compete with PGL-3 for mRNA (PMID:27594427). Supporting Evidence: PMID:17264081 Here we show that the TZF protein MEX-5, a primary anterior determinant, is an RNA-binding protein that recognizes linear RNA sequences with high affinity but low specificity. PMID:27594427 we show that competition between PGL-3 and MEX-5 for mRNA can regulate the formation of PGL-3 droplets. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5 is a non-enzymatic, cytoplasmic RNA-binding protein with **two CCCH zinc-finger domains** |
| GO:0003729 mRNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: mRNA binding is a core function of MEX-5, demonstrated by biochemical studies showing high-affinity binding to mRNA (PMID:17264081, PMID:27594427). InterPro-based inference is correct for this protein. Reason: This is a well-supported annotation. MEX-5 binds mRNA with high affinity through its tandem CCCH zinc fingers. Supporting Evidence: PMID:17264081 Here we show that the TZF protein MEX-5, a primary anterior determinant, is an RNA-binding protein that recognizes linear RNA sequences with high affinity but low specificity. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5/6 are **RNA-binding polarity mediators** that act largely through **translational control** and regulated association with RNA-containing complexes. Their CCCH zinc fingers are required for normal mobility/asymmetry |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is well-established for MEX-5 through multiple experimental studies. MEX-5 forms an anterior-enriched gradient in the cytoplasm. Reason: This is correct. MEX-5 is localized to the cytoplasm, with asymmetric enrichment in the anterior (PMID:10882103, PMID:18199581). Supporting Evidence: PMID:10882103 MEX-5 is a novel, cytoplasmic protein that is localized through PAR activities to the anterior pole of the 1-cell stage embryo. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5 is broadly cytoplasmic initially and becomes **anterior-enriched** by the end of the one-cell stage, contributing to preferential inheritance by the anterior AB blastomere. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: MEX-5 contains two CCCH-type zinc finger domains (positions 270-299 and 314-344 per UniProt), which coordinate zinc ions to form the RNA-binding structure. Reason: Zinc binding is intrinsic to the CCCH zinc finger fold. The two C3H1-type zinc fingers are annotated in UniProt and are essential for MEX-5's RNA-binding function. |
| GO:0017148 negative regulation of translation | IEA GO_REF:0000108 | ACCEPT | Summary: MEX-5 contributes to negative regulation of maternal mom-2 translation. Reason: The electronic inference is consistent with the retained translation-repressor function and primary 3′-UTR regulatory experiments. Positive zif-1 regulation does not exclude a negative effect on another RNA; the MEX-6 functional evidence is paired depletion plus conserved ancestral inference. Supporting Evidence: file:worm/mex-5/mex-5-primary-evidence.md The contrary is true for mom-2, where POS-1 promotes translation in P2 and MEX-5/6 represses translation in EMS. |
| GO:0043186 P granule | IEA GO_REF:0000117 | ACCEPT | Summary: MEX-5 is observed on granules in germline blastomeres. Reason: PMID:12588843 explicitly reports the GFP-tagged target on granules. The early anterior cytoplasmic gradient, granule dissolution activity and later germline granule pool are compatible. Cellular-component membership does not require a permanent structural scaffold. Supporting Evidence: file:worm/mex-5/mex-5-primary-evidence.md PIE-1:GFP, GFP:MEX-5 and GFP:MEX-6 all accumulated on granules in germline blastomeres. |
| GO:0046872 metal ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: MEX-5 contains CCCH zinc finger domains that bind zinc ions. Metal ion binding is a valid but generic annotation. Reason: This is correct - the CCCH zinc fingers coordinate zinc ions. GO:0008270 (zinc ion binding) is more specific and also annotated. |
| GO:0019901 protein kinase binding | IPI PMID:18199581 Polo kinases regulate C. elegans embryonic polarity via bind... | ACCEPT | Summary: PMID:18199581 demonstrates that MEX-5 (when phosphorylated on T186) binds to polo kinases PLK-1 and PLK-2 via their polo box domains. This is a direct experimental observation. Reason: PMID:18199581 provides direct experimental evidence for MEX-5 binding to polo kinases. This interaction is functionally significant for embryonic polarity. Supporting Evidence: PMID:18199581 We show that polo kinases, via their polo box domains, bind to and regulate the activity of two key polarity proteins, MEX-5 and MEX-6. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5/6 are required for **anterior enrichment of PLK-1 and PLK-2**, and PLK-1/2 bind MEX-5/6 via their **polo-box domains**. |
| GO:0019904 protein domain specific binding | IPI PMID:18199581 Polo kinases regulate C. elegans embryonic polarity via bind... | ACCEPT | Summary: MEX-5 binds specifically to the polo box domains of PLK-1 and PLK-2 when phosphorylated at T186. This is a legitimate domain-specific interaction. Reason: PMID:18199581 demonstrates that MEX-5 binds to polo kinases via their polo box domains, supporting the protein domain specific binding annotation. Supporting Evidence: PMID:18199581 polo kinases, via their polo box domains, bind to and regulate the activity of two key polarity proteins, MEX-5 and MEX-6. file:worm/mex-5/mex-5-deep-research-falcon.md Disrupting MEX-5–PLK binding impairs key MEX-5 activities (e.g., promoting PIE-1 degradation) without necessarily eliminating MEX-5 asymmetry, consistent with an adaptor/scaffold role rather than purely a localization effect. |
| GO:0032880 regulation of protein localization | IMP PMID:18199581 Polo kinases regulate C. elegans embryonic polarity via bind... | ACCEPT | Summary: MEX-5 regulates the asymmetric localization of multiple proteins including PLK-1, PIE-1, MEX-1, and POS-1 during early embryogenesis. This is extensively documented. Reason: This is a core function of MEX-5. MEX-5 establishes asymmetric distribution of germline proteins to the posterior by inhibiting their expression/localization in the anterior (PMID:10882103, PMID:18199581). Supporting Evidence: PMID:10882103 This network is required for subsequent asymmetries in the expression patterns of several proteins that are encoded by nonlocalized, maternally expressed mRNAs. PMID:18199581 This asymmetric localization of polo kinases depends on MEX-5 and MEX-6, as well as genes regulating MEX-5 and MEX-6 asymmetry. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5 recruits PLK-1 to the anterior, and a MEX-5 polo-docking site is required for PLK-1 to inhibit retention of posterior determinants |
| GO:0032880 regulation of protein localization | IGI PMID:18199581 Polo kinases regulate C. elegans embryonic polarity via bind... | ACCEPT | Summary: Same term as above but with IGI evidence code (genetic interaction). MEX-5 and MEX-6 work redundantly to regulate protein localization. Reason: The redundant function with MEX-6 is well-documented. MEX-5/MEX-6 double knockdown shows stronger phenotypes than single knockdowns. Supporting Evidence: PMID:10882103 We provide evidence that two nearly identical genes, mex-5 and mex-6, link PAR asymmetry to those subsequent protein asymmetries. |
| GO:0003730 mRNA 3'-UTR binding | IDA PMID:17264081 Molecular basis of RNA recognition by the embryonic polarity... | ACCEPT | Summary: PMID:17264081 demonstrates that MEX-5 binds to 3'-UTR sequences containing poly-U tracts. This is direct experimental evidence for 3'-UTR binding. Reason: PMID:17264081 shows MEX-5 recognizes poly-U tracts that are abundant in 3'-UTRs. The binding specificity studies were performed with RNA sequences. Supporting Evidence: PMID:17264081 This sequence is remarkably abundant in the 3'-untranslated region of C. elegans transcripts |
| GO:0005737 cytoplasm | IDA PMID:10882103 MEX-5 and MEX-6 function to establish soma/germline asymmetr... | ACCEPT | Summary: PMID:10882103 establishes that MEX-5 is a cytoplasmic protein localized to the anterior of the 1-cell embryo. This is primary experimental evidence. Reason: This is the original study characterizing MEX-5 localization. Direct observation of cytoplasmic localization. Supporting Evidence: PMID:10882103 MEX-5 is a novel, cytoplasmic protein that is localized through PAR activities to the anterior pole of the 1-cell stage embryo. |
| GO:0005737 cytoplasm | IDA PMID:12588843 Polarization of the C. elegans zygote proceeds via distinct ... | ACCEPT | Summary: PMID:12588843 confirms cytoplasmic localization of MEX-5 using GFP fusions and time-lapse microscopy during embryo polarization. Reason: Additional experimental confirmation of cytoplasmic localization with detailed localization dynamics. Supporting Evidence: PMID:12588843 Using time-lapse microscopy and GFP fusions, we have analyzed the localization dynamics of PAR-2, PAR-6, MEX-5, MEX-6 and PIE-1 in wild-type and mutant embryos. |
| GO:0008187 poly-pyrimidine tract binding | IDA PMID:17264081 Molecular basis of RNA recognition by the embryonic polarity... | ACCEPT | Summary: PMID:17264081 directly demonstrates that MEX-5 recognizes poly-uridine tracts (6+ U residues) as its binding site. This is high-quality experimental evidence for poly- pyrimidine tract binding. Reason: This is a core molecular function of MEX-5, directly demonstrated by biochemical studies. MEX-5 binds poly-U with high affinity (Kd ~10 nM). Supporting Evidence: PMID:17264081 The minimal binding site is a tract of six or more uridines within a 9-13-nucleotide window. file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5 exists in at least two effective mobility classes consistent with binding to RNA-containing complexes |
| GO:0043186 P granule | IDA PMID:12588843 Polarization of the C. elegans zygote proceeds via distinct ... | ACCEPT | Summary: MEX-5 is observed on granules in germline blastomeres. Reason: PMID:12588843 explicitly reports the GFP-tagged target on granules. The early anterior cytoplasmic gradient, granule dissolution activity and later germline granule pool are compatible. Cellular-component membership does not require a permanent structural scaffold. Supporting Evidence: file:worm/mex-5/mex-5-primary-evidence.md PIE-1:GFP, GFP:MEX-5 and GFP:MEX-6 all accumulated on granules in germline blastomeres. |
| GO:0005813 centrosome | IDA PMID:10882103 MEX-5 and MEX-6 function to establish soma/germline asymmetr... | ACCEPT | Summary: The experimentally curated centrosomal pool is retained. Reason: PMID:10882103 is the source IDA observation. A cytoplasmic concentration gradient does not exclude an additional centrosomal pool or justify demoting localization solely because it is not the predominant compartment. The abstract does not describe that imaging panel; retain the curator-supported localization without inventing a centrosome mechanism. Supporting Evidence: PMID:10882103 MEX-5 is a novel, cytoplasmic protein that is localized through PAR activities to the anterior pole of the 1-cell stage embryo. |
| GO:1903864 P granule disassembly | IMP PMID:27594427 Polar Positioning of Phase-Separated Liquid Compartments in ... | NEW | Summary: MEX-5 directly disassembles PGL-3/RNA condensates and patterns embryonic P granules. Reason: Retain this authored process proposal: MEX-5 does the work by binding RNA and altering the interactions that sustain the condensate. The 2016 reconstitution prevented assembly and modeled spatial segregation; the 2025 study directly demonstrates dissolution of preassembled condensates. The minimal tagged-protein/poly-rU assay does not establish that this mechanism alone accounts for every embryonic P-granule component. Supporting Evidence: PMID:40354522 we show that MEX-5 dissolves preassembled liquid-like PGL-3/RNA condensates by altering RNA availability and shifting the phase boundary. |
| GO:0008595 anterior/posterior axis specification, embryo | IMP PMID:10882103 MEX-5 and MEX-6 function to establish soma/germline asymmetr... | NEW | Summary: MEX-5 is essential for establishing anterior/posterior asymmetry in early C. elegans embryos, functioning downstream of PAR proteins to distribute germline determinants. Reason: Retain the existing proposal because the RNA-binding polarity regulators help execute spatial patterning of maternal determinants, not merely serve as a necessary substrate. PMID:10882103 establishes the link from PAR asymmetry to downstream protein asymmetry, and PMID:18199581 shows functional kinase recruitment. This axis-patterning process is distinct from the existing molecular binding and protein-localization terms. Supporting Evidence: PMID:10882103 We provide evidence that two nearly identical genes, mex-5 and mex-6, link PAR asymmetry to those subsequent protein asymmetries. PMID:12588843 Polarization of the C. elegans zygote along the anterior-posterior axis depends on cortically enriched (PAR) and cytoplasmic (MEX-5/6) proteins file:worm/mex-5/mex-5-deep-research-falcon.md MEX-5/6 are downstream effectors of PAR polarity that help segregate and/or regulate degradation of determinants (PIE-1, POS-1, MEX-1) and thereby influence early fate decisions |
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Download this section (compressed HTML)Q: What primary evidence underlies the UniProt DNA-binding keyword, and does MEX-5 directly bind DNA under physiological conditions?
Q: Which embryonic RNAs and protein partners mediate the inherited poly(A)-tail-shortening/adaptor role, as distinct from the experimentally demonstrated mom-2 repression and zif-1 activation?
Q: How do kinase state, MEG proteins and native RNA composition alter the MEX-5 condensate-disassembly mechanism observed in minimal reconstitution?
Experiment: Perform ribosome profiling/Ribo-seq to determine if MEX-5 directly affects translation. This would distinguish between MEX-5's proposed translation repression activity and its documented mRNA competition function.
Hypothesis: MEX-5 affects germline protein expression through P granule dissolution rather than direct translation repression
Experiment: Perform CLIP-seq to identify MEX-5 RNA targets genome-wide. This would validate the low-specificity binding model and identify which mRNAs MEX-5 competes for with PGL-3.
Hypothesis: MEX-5 binds promiscuously to most mRNAs containing poly-U tracts
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Download this section (compressed HTML)Actual PANTHER treeinfo POST response for PTHR12547 was traversed to the exact
accession-mapped target leaf. The extracted path, original positive IBD/IBA rows,
response size and SHA-256 are preserved in mex-5-paint-lineage.json.
Both MEX-5 and MEX-6 descend from PTN002648882, which supplies the five source IBAs
for AU-rich 3′-UTR binding, poly(A) tail shortening, translation repressor activity,
cytosol and protein-RNA sequence-specific adaptor activity. No target-lineage loss
was identified. Low specificity relative to TTP does not contradict preferential
recognition of U-rich RNA. Target inclusion among descendant evidence is legitimate,
not circular support. The paired paralogs have separate leaves and share this node.
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