A large-scale RNAi screen reveals that mitochondrial function is important for meiotic chromosome organization in oocytes

In prophase of the first meiotic division, chromatin forms a compact spherical cluster called the karyosome within the enlarged oocyte nucleus in Drosophila melanogaster. Similar clustering of chromatin has been widely observed in oocytes in many species including humans. It was previously shown that the proper karyosome formation is required for faithful chromosome segregation, but knowledge about its formation and maintenance is limited. To identify genes involved in karyosome formation, we carried out a large-scale cytological screen using Drosophila melanogaster oocytes. This screen comprised 3916 genes expressed in ovaries, of which 106 genes triggered reproducible karyosome defects upon knockdown. The karyosome defects in 24 out of these 106 genes resulted from activation of the meiotic recombination checkpoint, suggesting possible roles in DNA repair or piRNA processing. The other genes identified in this screen include genes with functions linked to chromatin, nuclear envelope, and actin. We also found that silencing of genes with mitochondrial functions, including electron transport chain components, induced a distinct karyosome defect typically with de-clustered chromosomes located close to the nuclear envelope. Furthermore, mitochondrial dysfunction not only impairs karyosome formation and maintenance, but also delays synaptonemal complex disassembly in cells not destined to become the oocyte. These karyosome defects do not appear to be mediated by apoptosis. This large-scale unbiased study uncovered a set of genes required for karyosome formation and revealed a new link between mitochondrial dysfunction and chromatin organization in oocytes.

Automated summary

During the prophase of the first meiotic division, chromatin forms a compact spherical cluster called the karyosome in the nucleus of the oocyte in Drosophila melanogaster. This phenomenon is also observed in oocytes of various species, including humans. A large-scale cytological screen was conducted to identify genes involved in karyosome formation using Drosophila melanogaster oocytes, leading to the discovery of 106 genes that triggered reproducible karyosome defects. These defects were found to be related to DNA repair, piRNA processing, chromatin, nuclear envelope, actin, and mitochondrial dysfunction. The study provides new insights into the formation and maintenance of the karyosome, and its implications in chromatin organization in oocytes.