Functional requirement for Dicer helicase arginine methylation in 26 G siRNA biogenesis and oocyte meiotic program.

Spatiotemporal regulation of Dicer is essential for small RNA biogenesis and fertility, yet how its helicase domain is controlled remains unclear. Using Caenorhabditis elegans, we identify a regulatory role for the arginine-rich GRARR motif within helicase domain motif VI of DCR-1. Mutating conserved arginines in this sequence disrupts maternal 26 G endo-siRNA production, impairs oocyte meiosis I and II, and reduces fertility. Biochemically, an asymmetrically dimethylated DCR-1 GRA[R495*]R peptide enhances interaction with ERI-5, a tandem-Tudor protein in the ERIC complex, while loss of DCR-1(R495) diminishes this interaction in vivo. Genetically, eri-5 deletion phenocopies the dcr-1 R495K mutant, supporting a functional partnership in 26 G siRNA biogenesis. Notably, these defects parallel those seen in DCR-1 phosphorylation mutants in the catalytic domain. AlphaFold modeling suggests that arginine methylation in the helicase domain and serine phosphorylation in catalytic domain may operate in a coordinated manner to modulate DCR-1 conformation, effector recruitment, and proper execution of the oocyte meiotic program.