PMID:36196602

Specialized germline P-bodies are required to specify germ cell fate in Caenorhabditis elegans embryos.

MEG-1 and MEG-2 are intrinsically-disordered proteins distantly related to the MEG-3/MEG-4 P-granule scaffolds, originally described as P granule proteins; here they are shown to associate with canonical P-body proteins and stabilize germline P-body condensates in P4.

"MEG-1 and MEG-2 are two intrinsically-disordered proteins, distantly related to MEG-3 and MEG-4, and originally described as P granule proteins"
MEG-1/MEG-2 associate with canonical P-body proteins and stabilize P-body-like condensates specifically in the germline founder cell P4.

"we demonstrate that MEG-1 and MEG-2 associate with canonical P-body proteins and stabilize P-body-like condensates in P4"
Germline P-bodies, unlike P granules, contain regulators of mRNA decapping and deadenylation plus MEG-1, MEG-2 and the RNA-binding protein POS-1.

"Like canonical P-bodies found in somatic cells, 'germline P-bodies'"
Embryos lacking meg-1 and meg-2 fail to stabilize P-body components, misregulate POS-1 targets, mis-specify the germline founder cell, and do not develop a germline.

"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."
MEG-1 enriches at the periphery of P granules in P1-P3 blastomeres, merges with P granules in P4, and becomes cytoplasmic and degraded in Z2/Z3.

"MEG-1 enriches at the periphery of P granules in the P1-3 blastomeres, and merges with P granules in P4"
In the primordial germ cells Z2 and Z3, MEG-1 becomes cytoplasmic and is degraded, while P granules remain.

"In the primordial germ cells Z2 and Z3, MEG-1 becomes cytoplasmic and is degraded, while P granules remain"
By high-resolution imaging, MEG-1 puncta in P4 correspond to germline P-bodies, condensates distinct from P granules that colocalize with the P-body markers CGH-1 (DDX6) and EDC-3 and enrich deadenylated mRNAs.

"MEG-1 puncta in P4 correspond to germline P-bodies"
meg-1 and meg-2 are required redundantly to maintain CGH-1 and EDC-3 levels and to assemble robust germline P-bodies in the germline founder cell P4.

"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

Falcon deep research report on C. elegans meg-1 (Q21126)

The current model places MEG-1/MEG-2 not as core P-granule scaffolds (a role of MEG-3/MEG-4) but as organizers of a distinct germline P-body condensate required for germ cell fate specification.

"**MEG-1/MEG-2** are now associated with a **germline P-body-like condensate** that is distinct from canonical **P granules**, which are largely scaffolded by MEG-3/MEG-4."
meg-1 mutants can assemble P granules but show defects in P-granule disassembly and segregation, with anterior P1 granules failing to disassemble and being mis-inherited by somatic blastomeres.

"meg-1 mutants can assemble P granules but show defects in **P-granule disassembly and segregation**"
MEG-1::GFP immunoprecipitation identified 54 enriched proteins including decapping/deadenylation (P-body) factors and post-transcriptional regulators, with POS-1 among the most highly enriched interactors.

"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**."
meg-1 interacts genetically with nanos family members: nos-3 loss suppresses meg-1 sterility, whereas nos-2 loss enhances meg-1 defects.

"- **nos-3 loss suppresses meg-1 sterility** - **nos-2 loss enhances meg-1 defects**, including severe proliferation/survival outcomes"
In severe combinatorial meg mutants, meg-1;meg-3;meg-4 larvae had fewer than 10 germ cells and were 100% sterile.

"meg-1;meg-3;meg-4 larvae had **<10 germ cells** and were **100% sterile**"

PMID:18202375

MEG-1 and MEG-2 are embryo-specific P-granule components required for germline development in Caenorhabditis elegans.

MEG-1 and MEG-2 are P granule components expressed in maternal germline

"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"
MEG proteins localize exclusively to P granules during embryonic germline segregation

"encode proteins that localize exclusively to P granules during embryonic germline segregation"
MEG-1 localization depends on membrane-bound MES-1 protein

"Localization of MEG-1 to P granules depends upon the membrane-bound protein MES-1"
meg-1 mutants show P granule mis-segregation, underproliferation, aberrant morphology, and sterility

"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"
meg-1 provides critical link for germline continuity between generations

"it provides a critical link for ensuring the continuity of germline development from one generation to the next"

PMID:25535836

Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans.

MEG proteins are intrinsically disordered, serine-rich proteins

"a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos"
MEG-1 and MEG-3 are substrates of MBK-2/DYRK kinase and PP2A phosphatase

"MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A"
Phosphorylation promotes P granule disassembly; dephosphorylation promotes assembly

"Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly"
MEG proteins are required redundantly for fertility

"The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility"
P granules are non-homogeneous structures regulated by phosphorylation

"despite their liquid-like behavior, P granules are non-homogeneous structures whose assembly in embryos is regulated by phosphorylation"

PMID:21305687

C. elegans meg-1 and meg-2 differentially interact with nanos family members to either promote or inhibit germ cell proliferation and survival.

MEG-1 may function with NOS-2 and NOS-3 to promote germ cell proliferation
MEG-1 and MEG-2 have differential genetic interactions with nanos family members

file:worm/meg-1/meg-1-uniprot.txt

UniProt entry for MEG-1 (Q21126)

MEG-1 interacts with PPTR-1, PPTR-2, and PGL-1

"Interacts with pptr-1, pptr-2 and pgl-1"
In dephosphorylated form promotes P granule assembly in posterior cytoplasm

"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"
Double knockdown of meg-1 and meg-2 causes P granule disassembly defects

"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"