MEG-1 (maternal-effect germ cell defective 1; K02B9.1, UniProt Q21126) is an intrinsically disordered, serine-rich protein of the germ plasm in C. elegans embryos, encoded maternally and expressed in the P (germline) lineage from the 4-8 cell stage, with expression diminishing at the 100-cell stage. It is distantly related to, but functionally distinct from, the MEG-3/MEG-4 scaffold pair: whereas MEG-3/MEG-4 form the nanoscale clusters that scaffold and protect the PGL-1/PGL-3 P-granule core, MEG-1 (acting partially redundantly with its paralog MEG-2) associates with canonical P-body proteins (decapping and deadenylation factors) and is now understood to organize a SECOND, distinct germ-plasm condensate, the 'germline P-body', rather than to act as a core P-granule scaffold itself (Cassani & Seydoux 2022, PMID:36196602; Chiappetta et al. 2022 review). MEG-1 enriches at the periphery of P granules in the P1-P3 blastomeres and merges with perinuclear P granules in P4, then becomes cytoplasmic and is degraded in the primordial germ cells Z2/Z3. MEG-1/MEG-2-dependent germline P-bodies stabilize P-body components and regulate maternal mRNAs (including POS-1 targets), and are required to specify P4 as the germline founder cell; embryos lacking meg-1 and meg-2 mis-specify P4 and fail to develop a germline. MEG-1 is also a substrate of the MBK-2/DYRK kinase and the PP2A phosphatase complex (PPTR-1/PPTR-2): its phosphorylation state regulates P-granule phase transitions, with phosphorylation promoting disassembly of zygotic P granules in anterior cytoplasm and dephosphorylation promoting assembly/accumulation in posterior cytoplasm. Loss of meg-1 causes P-granule mis-segregation, underproliferation and aberrant morphology of larval germ cells, and maternal-effect sterility; it interacts genetically with the nanos family members nos-2 and nos-3. MEG-1 localization to P granules depends on the membrane-bound protein MES-1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0036093 germ cell proliferation | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: MEG-1 is required for germ cell proliferation during larval development. meg-1 mutants show underproliferation of germ cells (PMID:18202375). The IGI annotation with meg-3 and meg-4 reflects that MEG proteins contribute redundantly to germ cell viability and proliferation (PMID:25535836, PMID:21305687). MEG-1 may function with nanos family members nos-2 and nos-3 to promote germ cell proliferation. Reason: This annotation is well-supported by multiple publications. PMID:18202375 states that meg-1 mutants exhibit underproliferation in larval germ cells. PMID:25535836 demonstrates that MEG proteins are required redundantly for fertility and germ cell development. The IGI evidence from genetic interactions with other MEG family members is appropriate. Supporting Evidence: PMID:18202375 meg-1 mutants exhibit multiple germline defects: P-granule mis-segregation in embryos, underproliferation and aberrant P-granule morphology in larval germ cells, and ultimately, sterility as adults PMID:25535836 The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility PMID:36196602 Embryos lacking meg-1 and meg-2 do not stabilize P-body components, misregulate POS-1 targets, mis-specify the germline founder cell and do not develop a germline. file:worm/meg-1/meg-1-deep-research-falcon.md Z2/Z3 primordial germ cells are present at hatching, but later larval germ-cell proliferation fails; blocking apoptosis (**ced-4**) does not rescue the loss, arguing against canonical apoptosis as the main cause. |
| GO:1903864 P granule disassembly | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: MEG-1 in its phosphorylated form promotes P granule disassembly in the anterior cytoplasm of pre-gastrulation embryos. This is a key function of MEG proteins - phosphorylation by MBK-2 promotes granule disassembly while dephosphorylation promotes assembly (PMID:25535836). The annotation is supported by the finding that MEG-1 and MEG-2 knockdown results in defective P granule disassembly in anterior cytoplasm. Reason: This annotation accurately captures a specific aspect of MEG-1 function. The phosphorylated form of MEG-1 promotes P granule disassembly. While MEG-1 also promotes assembly in its dephosphorylated form, the disassembly annotation is correct and well-supported by experimental evidence showing defective disassembly upon MEG-1/MEG-2 knockdown. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly file:worm/meg-1/meg-1-uniprot.txt Simultaneous RNAi-mediated knockdown of meg-1 and meg-2 results in defects in P granule disassembly in the anterior cytoplasm of the P1 blastomere causing some P granules to be mis-segregated to somatic blastomeres file:worm/meg-1/meg-1-deep-research-falcon.md meg-1 mutants can assemble P granules but show defects in **P-granule disassembly and segregation** file:worm/meg-1/meg-1-deep-research-falcon.md Genetic interactions place meg genes in pathways regulating granule disassembly involving **MBK-2** kinase and **PPTR-1/2** phosphatase components. |
| GO:0005515 protein binding | IPI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | MODIFY | Summary: MEG-1 has documented physical interactions with PPTR-1, PPTR-2 (PP2A regulatory subunits), and PGL-1 (a P granule component) based on PMID:25535836. However, 'protein binding' (GO:0005515) is an uninformative annotation that does not describe the molecular function. Reason: GO curation guidelines recommend avoiding generic 'protein binding' annotations when more specific terms are available. The three IPI WITH/FROM partners underlying this GOA annotation (UniProtKB:A9UJN4, O18178, Q304E5) correspond to the documented PPTR-1, PPTR-2 (PP2A regulatory subunits) and PGL-1 (P-granule) interactions. protein phosphatase binding (GO:0019903) captures the PP2A interaction that is mechanistically central to MEG-1 phosphoregulation. Falcon proteomics further shows MEG-1::GFP co-purifies a broad post-transcriptional regulator interactome (decapping/deadenylation and CCR4-NOT factors, plus POS-1, GLD-1/2/3, OMA-1, MEX-1/3, SPN-4), consistent with a molecular adaptor / condensate-organizing role rather than a single specific binding partner. Retaining GO:0019903 as a replacement is defensible; the broader adaptor role is captured in core_functions. Proposed replacements: protein phosphatase binding Supporting Evidence: file:worm/meg-1/meg-1-uniprot.txt Interacts with pptr-1, pptr-2 and pgl-1 PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. file:worm/meg-1/meg-1-deep-research-falcon.md MEG-1::GFP immunoprecipitation identified **54 enriched proteins** (>=2-fold), including canonical **P-body / mRNA-decay factors** such as **DCAP-2/DCP2, EDC-4**, CCR4-NOT-related subunits (**NTL-1, TAG-153, NTL-3**), **IFET-1**, and regulators **GLD-1, GLD-2, GLD-3, MEX-1, OMA-1, POS-1, MEX-3, SPN-4**. |
| GO:0043186 P granule | IDA PMID:18202375 MEG-1 and MEG-2 are embryo-specific P-granule components req... | ACCEPT | Summary: MEG-1 localizes to P granules during embryonic germline segregation. This is a core finding from PMID:18202375 where MEG-1 and MEG-2 were first characterized as P granule components. The protein is expressed in the P lineage from the 4-8 cell stage and localizes exclusively to P granules during this developmental window. Reason: This is a well-supported cellular component annotation with direct experimental evidence (IDA). PMID:18202375 demonstrates that MEG-1 localizes to P granules during embryonic germline segregation, with localization depending on MES-1. Higher-resolution imaging (Cassani & Seydoux 2022, PMID:36196602) refines this: MEG-1 enriches at the PERIPHERY of P granules in P1-P3 and merges with perinuclear P granules in P4, before becoming cytoplasmic and being degraded in Z2/Z3. MEG-1 also marks an apposed germline-P-body condensate distinct from the PGL/MEG-3 P-granule core; the P granule localization remains correct but is not exclusive to the canonical P-granule core. The annotation is retained as ACCEPT. Supporting Evidence: PMID:18202375 meg-1 and meg-2 (maternal-effect germ-cell defective), which are expressed in the maternal germline and encode proteins that localize exclusively to P granules during embryonic germline segregation PMID:18202375 Localization of MEG-1 to P granules depends upon the membrane-bound protein MES-1 PMID:36196602 MEG-1 enriches at the periphery of P granules in the P1-3 blastomeres, and merges with P granules in P4 file:worm/meg-1/meg-1-deep-research-falcon.md MEG-1 localizes to **embryonic P granules** from the **2-cell stage through ~100-cell stage** |
| GO:0000932 P-body | IDA PMID:36196602 Specialized germline P-bodies are required to specify germ c... | NEW | Summary: MEG-1 localizes to a germline P-body condensate, distinct from but apposed to the canonical PGL/MEG-3 P granule. High-resolution imaging shows MEG-1 puncta in P4 correspond to germline P-bodies that colocalize with the P-body markers CGH-1 (DDX6) and EDC-3 and contain deadenylated mRNAs. This is the central reframing of Cassani & Seydoux 2022 (PMID:36196602): MEG-1's home condensate is the germline P-body rather than the canonical P granule. Reason: Cassani & Seydoux 2022 (PMID:36196602) demonstrate by direct imaging (IDA) that MEG-1 marks germline P-bodies - assemblies distinct from P granules that colocalize with canonical P-body markers (CGH-1/DDX6, EDC-3) and enrich deadenylated mRNAs. This CC annotation more precisely captures MEG-1's localization than the P granule term alone. The existing GO:0043186 (P granule) annotation is retained, since MEG-1 does associate with the P-granule periphery and merges with P granules in P4. Supporting Evidence: PMID:36196602 MEG-1 puncta in P4 correspond to germline P-bodies PMID:36196602 we demonstrate that MEG-1 and MEG-2 associate with canonical P-body proteins and stabilize P-body-like condensates in P4 |
| GO:1903863 P granule assembly | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | NEW | Summary: MEG-1 in its dephosphorylated form promotes P granule assembly in the posterior cytoplasm. This annotation is missing from the existing GOA annotations but is equally supported by the literature as P granule disassembly. PMID:25535836 clearly states that dephosphorylated MEG proteins promote assembly. Reason: The current annotations include P granule disassembly but not P granule assembly, despite MEG-1 being involved in both processes depending on phosphorylation state. This annotation should be added to provide a more complete picture of MEG-1 function. Note that MEG-1 CONTRIBUTES to P granule assembly/accumulation (in its dephosphorylated form, together with MEG-2) but is not strictly required for canonical PGL/MEG-3 condensate formation: Cassani & Seydoux 2022 (PMID:36196602) show that MEG-3 and PGL-3 still assemble into puncta that segregate with P blastomeres in meg-1 meg-2 mutants, with only a minor contribution of MEG-1/2 to P granule segregation. The annotation is therefore retained as a NEW non-core involvement rather than an essential assembly role. Supporting Evidence: file:worm/meg-1/meg-1-uniprot.txt In its dephosphorylated form, and together with meg-2, promotes the assembly and accumulation of zygotic P granules in the posterior cytoplasm of pre-gastrulation embryos PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly |
| GO:0030719 P granule organization | IGI PMID:36196602 Specialized germline P-bodies are required to specify germ c... | NEW | Summary: MEG-1, redundantly with MEG-2, organizes germline RNP condensates in the embryonic P lineage. Rather than scaffolding the canonical PGL/MEG-3 P-granule core (a role of MEG-3/MEG-4), MEG-1/MEG-2 nucleate and stabilize an apposed germline P-body enriched for decapping and deadenylation machinery, and contribute to phosphorylation-dependent assembly/disassembly and asymmetric segregation of P granules. This higher-level organization term captures MEG-1's condensate-organizing role. Reason: Core function term capturing the condensate-organizing role of MEG-1 that is not represented by the more specific assembly/disassembly terms alone. Cassani & Seydoux 2022 (PMID:36196602) provide directly traceable genetic-interaction evidence: meg-1 meg-2 double mutants fail to maintain CGH-1 and EDC-3 and fail to assemble robust germline P-bodies in P4. The evidence code is IGI (genetic interaction with the paralog meg-2), reflecting the redundant action of MEG-1/MEG-2 demonstrated by the double-mutant phenotype; this is stronger and more traceable than the prior NAS code. Supporting Evidence: PMID:36196602 meg-1 and meg-2 are required to maintain CGH-1 and EDC-3 and assemble robust germline P-bodies in P4 file:worm/meg-1/meg-1-deep-research-falcon.md MEG-1/2 nucleate a **germline P-body** distinct from, but often adjacent to, P granules, enriched for **decapping and deadenylation enzymes**. PMID:36196602 we demonstrate that MEG-1 and MEG-2 associate with canonical P-body proteins and stabilize P-body-like condensates in P4 |
| GO:0060090 molecular adaptor activity | IC | NEW | Summary: MEG-1 is an intrinsically disordered protein with no known catalytic activity. Its documented molecular role is to bring together other molecules - P-body decapping/deadenylation machinery and post- transcriptional regulators (POS-1, GLD-1/2/3, OMA-1, MEX-1/3, SPN-4) plus the PP2A phosphatase subunits PPTR-1/PPTR-2 - to nucleate and stabilize a germline P-body condensate, consistent with molecular adaptor activity. Reason: Captures the molecular function inferred from MEG-1's interactome and condensate-organizing role. Inferred by curator (IC) from the P granule organization annotation and the MEG-1::GFP proteomics / germline P-body model; MEG-1 brings multiple post-transcriptional regulators together without itself having catalytic activity. Not asserted as a primary experimental annotation, hence IC rather than IDA. Supporting Evidence: PMID:36196602 we demonstrate that MEG-1 and MEG-2 associate with canonical P-body proteins and stabilize P-body-like condensates in P4 file:worm/meg-1/meg-1-deep-research-falcon.md MEG-1::GFP immunoprecipitation identified **54 enriched proteins** (>=2-fold), including canonical **P-body / mRNA-decay factors** such as **DCAP-2/DCP2, EDC-4**, CCR4-NOT-related subunits (**NTL-1, TAG-153, NTL-3**), **IFET-1**, and regulators **GLD-1, GLD-2, GLD-3, MEX-1, OMA-1, POS-1, MEX-3, SPN-4**. |
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Download this section (compressed HTML)Q: What is the precise mechanism by which phosphorylation of MEG-1 promotes P granule disassembly in anterior cytoplasm?
Suggested experts: Geraldine Seydoux
Q: How does MEG-1 coordinate with MEG-2, MEG-3, and MEG-4 to regulate P granule dynamics and germ cell fate?
Suggested experts: Valerie Reinke, Geraldine Seydoux
Experiment: Use lattice light sheet microscopy to track GFP-MEG-1 dynamics during early embryonic cell divisions with and without MBK-2 kinase activity
Hypothesis: Phosphorylation by MBK-2 causes MEG-1 to dissociate from P granules in anterior cytoplasm, promoting their disassembly
Type: Time-lapse imaging
Experiment: Identify all phosphorylation sites on MEG-1 and determine which are regulated by MBK-2 vs PP2A using mass spectrometry
Hypothesis: Multiple serine residues in MEG-1's disordered regions are differentially phosphorylated to regulate granule dynamics
Type: Phosphoproteomics
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