Centrosomes are critical sites for orchestrating microtubule behavior and exhibit dynamic changes in size during the cell cycle. As cell cycle progresses to mitosis, centrosomes recruit more microtubules to form bipolar spindles that ensure accurate chromosome segregation. The szy-20 gene encodes a conserved RNA-binding protein that negatively regulates centrosome duplication by opposing ZYG-1, a key centrosome duplication factor. Centrosomes in szy-20 mutants exhibit elevated levels of centrosomal proteins, resulting in defective microtubule dynamics and embryonic lethality. SZY-20 contains putative RNA-binding domains (SUZ, SUZ-C): mutating these domains has been shown to perturb in vitro RNA-binding of SZY-20 and its capacity to regulate centrosome size in vivo. Despite the finding that SZY-20 negatively regulates ZYG-1, no direct interaction between the two proteins has been found. Thus, identifying additional factors that function between SZY-20 and ZYG-1 should provide further insights into the molecular mechanism by which the RNA-binding protein SZY-20 influences centrosome assembly.
Toward this end, we identified an RNA-binding protein, ATX-2, that physically associates with SZY-20. ATX-2 is the C. elegans ortholog of human Ataxin-2 that is implicated in human neurodegenerative disease. We show a new role for ATX-2 in regulating centrosome size and microtubule dynamics. Depletion of ATX-2 results in embryonic lethality and cytokinesis failure in wild type embryos, and restores centrosome duplication to zyg-1mutants. ATX-2 forms a complex with SZY-20 in an RNA-independent fashion. In this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with centrosome size. Centrosomes in atx-2 mutants exhibit elevated levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin), increasing microtubule nucleating activity but hindering microtubule growth. We show that ATX-2 influences microtubule behavior by regulating the microtubule nucleating factor γ-Tubulin and microtubule destabilizer KLP-7. Our data suggest that RNA-binding proteins play an active role in controlling microtubule dynamics and provide insight into the control of proper centrosome size and microtubule behavior.