Ataxin-2 regulates the synaptonemal complex to ensure chromosome pairing during female meiosis

Abstract Sexual reproduction relies on meiotic recombination and the accurate segregation of homologous chromosomes to generate viable, genetically diverse gametes. While the molecular mechanisms of recombination and chromosome segregation are well studied, the upstream regulatory cues that drive expression of key meiotic genes remain poorly understood, especially in metazoans. Emerging evidence suggests that posttranscriptional regulation plays a central role in initiating and coordinating the meiotic program in both fruit flies and mammals. Here, we identify the RNA-binding protein Ataxin-2 (Atx2) as a crucial regulator of meiosis in Drosophila melanogaster. We show that Atx2 positively regulates meiotic factors, especially components of the synaptonemal complex (SC), a structure essential for pairing, recombination, and segregation of homologous chromosomes. In Atx2-depleted germ cells, SC component mRNA and protein levels are markedly reduced, leading to defective SC assembly and maintenance. Consequently, homologous chromosomes fail to pair properly, which is essential for proper homolog segregation and the prevention of aneuploidy. These findings uncover Atx2 as a key regulator of the SC and highlight an underappreciated layer of gene regulation essential for accurate meiotic chromosome segregation and fertility.