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<p>Spatiotemporal regulation of Dicer is essential for small RNA biogenesis and fertility, yet how its helicase domain is controlled remains unclear. Using <i>Caenorhabditis elegans</i>, 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, <i>eri-5</i> deletion phenocopies the <i>dcr-1</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Nick Newkirk,
  • Shin-Yu Chen,
  • Tokiko Furuta,
  • Kenneth A. Trimmer,
  • Leilei Shi,
  • Sabrina Stratton,
  • Hongyuan Li,
  • Xiaodong Cheng,
  • Mark T. Bedford,
  • Swathi Arur

摘要

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.