PMID:25535836

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

MEG proteins (MEG-1, MEG-3, MEG-4) are IDPs that regulate P granule dynamics

"we present evidence that a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos"
MEGs are substrates of MBK-2/DYRK kinase and PP2A phosphatase

"We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A(PPTR-½)"
Phosphorylation promotes granule disassembly, dephosphorylation promotes assembly

"Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly"
GFP-MEG-3 localizes to dynamic domain surrounding P granules

"GFP-tagged MEG-3 localizes to a dynamic domain that surrounds and penetrates each granule"
MEG proteins function redundantly for fertility

"The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility"

file:worm/meg-4/meg-4-deep-research-falcon.md

Falcon deep research report on C. elegans meg-4 (Q9TZK8 / C36C9.1)

MEG-4 acts redundantly with its close paralog MEG-3 to drive cytoplasmic (embryonic) P granule assembly and to promote preferential germline inheritance/enrichment of maternal mRNAs during early embryogenesis.

"acts **redundantly with its close paralog MEG-3** to drive **cytoplasmic (embryonic) P granule assembly**"
MEG-4 is a large (832 aa), serine/threonine-rich, largely intrinsically disordered MEG-family protein (~69% predicted disorder, 570/832 aa) with low-complexity regions, consistent with a condensate scaffold/regulator role.

"MEG-4 is predicted to be largely disordered (**~69% predicted disorder; 570/832 aa**)"
MEG-3 and MEG-4 are approximately 71% identical and functionally redundant in embryonic P granule assembly.

"MEG-3 and MEG-4 are reported as **~71% identical** and functionally redundant in embryonic P granule assembly."
MEG-4 is maternally provided and associates with embryonic P granules / germ plasm from the 1-cell through ~100-cell stage, segregating with the P lineage; a CRISPR C-terminal 3xFLAG tag was used to localize MEG-4.

"MEG-4 is maternally provided and associates with embryonic P granules from the **1-cell through ~100-cell stage**, segregating with the P lineage."
In meg-3 meg-4 double mutant zygotes, granule formation is severely impaired; total P granules during first mitosis are reduced to ~11% of wild-type, and nos-2 mRNA segregates symmetrically rather than with the germline blastomere.

"total P granules in meg-3 meg-4 zygotes are reduced to **~11% of wild-type**."
Genetic epistasis places meg-3/meg-4 downstream of the kinase MBK-2/DYRK and PP2A regulatory subunits PPTR-1/2 in controlling the balance of P granule assembly and disassembly.

"Genetic epistasis places *meg-3/meg-4* downstream of the kinase **MBK-2/DYRK** and PP2A regulatory subunits **PPTR-1/2** for controlling P granule assembly/disassembly."
meg-3/4-dependent P granules contribute to preferential germline enrichment/inheritance of particular maternal mRNAs (e.g. nos-2).

"MEG-3/4-dependent P granules contribute to **preferential germline enrichment/inheritance** of particular maternal mRNAs."
meg-4 single mutants show only a slight reduction in P granule number; the meg-3 meg-4 double mutant has the strongest embryonic assembly defect, indicating redundancy with MEG-3 contributing the larger share.

"*meg-4* single mutants show **only a slight reduction** in P granule number in zygotes"
MEG-1/MEG-3/MEG-4 are required for cytoplasmic but not perinuclear P granule formation; perinuclear granules reappear later (L1/L4), indicating a stage-specific requirement.

"**meg-1, meg-3, and meg-4 are required for cytoplasmic but not perinuclear P granule formation**"
meg-1 meg-3 meg-4 triple mutants are 100% sterile with larvae showing <10 germ cells and failure of germ cell proliferation, indicating MEG proteins contribute redundantly to germline development.

"**meg-1 meg-3 meg-4** animals are reported as **100% sterile**, with larvae exhibiting **<10 germ cells** and failure of germ cell proliferation."
The peer-reviewed literature does not support the UniProt "J domain-containing protein" name for MEG-4; no source describes MEG-4 as an Hsp40/J-domain co-chaperone or reports J-domain-dependent activities.

"none of these sources describe MEG-4 as an Hsp40/J-domain co-chaperone or report J-domain-dependent activities"