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Functional Requirement for Arginine Methylation of the Dicer Helicase Domain in 26G Endo-siRNA Pathway Activity and the Oocyte Meiotic Program

ABSTRACT: Spatiotemporal regulation of Dicer is critical for small RNA biogenesis, fertility, and early embryogenesis, yet, the mechanisms that modulate its activity, especially through the helicase domain, remain incompletely understood. Here, we identify regulatory roles for a non-traditional glycine-arginine-rich (GAR) motif, GRARR, in motif VI of the helicase domain. Mutations to conserved arginine residues of the GRARR motif impair maternal 26G endo-siRNA production and disrupt oocyte-to-embryo transition. We show that asymmetric di-methylation of Dicer R495 within this motif facilitates binding to ERI-5, a tandem-Tudor protein within the ERI Complex, likely potentiating 26G siRNA biogenesis, as deletion of eri-5 Tudor domains phenocopies Dicer GRARR mutants. Notably, these phenotypes are similar to those observed in Dicer phosphorylation mutants, implicating both arginine methylation and serine phosphorylation function in a coordinated mechanism. Our findings propose that a post-translational modification switch modulates Dicer conformation and effector engagement to control endo-siRNA production and oocyte-to-embryo transition.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE300966 | GEO | 2026/04/01

REPOSITORIES: GEO

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	GSE300966_HQAlign_readmappings.xlsx	Xlsx
	GSE300966_tinyrna_cond1_G1685D_cond2_WT_deseq_table.csv.gz	Csv
	GSE300966_tinyrna_cond1_R3K_cond2_WT_deseq_table.csv.gz	Csv

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