Phosphorylation of the Argonaute ALG-1 regulates microRNA binding during C. elegans development

Here, we report a new phosphorylation site on ALG-1 that modulates its ability to bind miRNAs. Mutating ALG-1 S642 into a phosphomimetic residue strongly impairs binding to miRNAs. Furthermore, this mutation causes embryonic lethality which are not observed in animals depleted of alg-1 suggesting that it may consequently impair the normal function of its homolog alg-2. Quantification of miRNAs in the phosphorylation mutants of alg-1 reveals that the miRNA passenger strands are strongly increased but not preferentially loaded into ALG-1, indicating that the defects in miRNA binding may also lead to an accumulation of miRNA duplexes. Quantification of miRNA expression in Alg1 mutants.