Homologous chromosome pairing in meiosis

• Applicant: Dr. Simone Köhler
• Subject Area: Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495429102

For sexual reproduction, most eukaryotes rely on meiosis, the specialized cell division process that generates haploid gametes from diploid precursor cells. This process relies on faithful pairing, synapsis, recombination and segregation of homologous chromosomes from both parents. Even though errors in pairing and synapsis cause severe congenital disorders or infertility, the central question of how homologs pair during meiotic prophase remains open. In C. elegans, homologous pairing is largely mediated by specific chromosomal regions (pairing centers) that recruit specific proteins (pairing center proteins). However, only four different proteins mediate pairing of six different chromosomes, which raises the question of how homologs first recognize each other. Our lab recently discovery that RNA plays a role in homologous pairing in C. elegans. We showed that RNA molecules enriched in pairing center specific sequences are localized at sites of homologous chromosome pairing and are required for robust and timely pairing. Excited by this still unpublished finding, we here propose to systematically analyze the role of RNAs during homologous chromosome pairing which is critical for the success of meiosis. To this end, we aim to first identify which specific RNA molecules are localized at sites of homologous chromosome pairing in C. elegans using next generation sequencing approaches (Tag-seClip-seq or RNAseq). We will then use genome engineering and cytological as well as genetic studies to directly test the function of these RNAs for homologous chromosome pairing. To address how these RNA molecules interact with pairing center proteins to ensure accurate pairing of homologous chromosomes, we will use biochemical, bioinformatic and genetic tools. These studies will be accompanied by ultrastructural analysis in situ at super-resolution which will shed light on how chromatin, proteins and RNA interact to mediate homologous pairing. We anticipate that the results of this study will shed new light on the key open question in the field, namely how chromosomes can recognize homology.

• DFG Programme: Research Grants