Akulenko, N., Olenkina, O., Mikhaleva, E., Marfina, S., Krylova, A., Toshchakov, S., Ryazansky, S. (2025). Dora, a key component of target-directed miRNA degradation, is essential for local genomic amplification in Drosophila ovarian follicle cells.  Gene 965(): 149677.

FBrf0263114

Research paper

The ubiquitin ligase receptor Dora, the Drosophila homolog of ZSWIM8, is a key component of the target-directed microRNA degradation (TDMD) pathway. Previous studies have implicated TDMD - and, consequently, ZSWIM8/Dora - in various developmental processes. Here, we investigate the role Dora plays in Drosophila oogenesis, focusing on ovarian somatic cells. We generated a fly strain with an endogenously tagged Dora protein and observed its presence in both germline and somatic follicular cells of the ovaries. Somatic knockdown of dora revealed its essential role in normal eggshell formation. Specifically, Dora loss led to reduced chorion and vitelline transcript levels and decreased chorion gene amplification, both of which are critical for eggshell protein production. Somatic depletion of Dora reduces the Cut protein levels but did not affect the abundance of other known regulators of eggshell formation, including Ttk69, miR-7 or miR-318 indicating that Dora functions independently of these pathways. Although a direct link between TDMD and chorion eggshell development remains to be confirmed, our findings clearly highlight Dora as a critical regulator in this process. These results pave the way for further investigation into the specific role of TDMD and provide new insights into the regulatory mechanisms underlying animal oogenesis.