Biology subjects

Uebel, C. J.

Publications and source records attributed to Uebel, C. J..

3 recordsLinked to original sources

bioRxiv2026

Disordered protein COSA-2 maintains crossover-specific repair compartments to ensure meiotic crossover maturation

Faithful genome inheritance during meiosis relies on crossover repair of double-strand DNA breaks (DSBs) to connect homologous chromosomes and direct their proper segregation. The formation of crossover-specific recombination intermediates and accumulation of pro-crossover factors occurs at an extremely limited subset of DSB sites, necessitating that the subset of recombination sites designated to become crossovers reliably mature into crossovers. Here we identify C. elegans disordered protein COSA-2 as crucial for meiotic crossover maturation. COSA-2 abruptly concentrates at crossover intermediates in late pachytene nuclei, where it colocalizes and associates with other pro-crossover factors. COSA-2 is dispensable for early loading of crossover factors and for crossover designation, but is required for maintenance of pro-crossover factors at crossover-designated sites and for focal enrichment of factors initially distributed throughout the synaptonemal complex. We define a COSA-2 execution point during late pachytene wherein crossover intermediates transition from a vulnerable state (in which they require COSA-2 to avoid being dismantled) to a state where COSA-2 and local crossover-factor enrichment are no longer required to connect homologs. We propose that COSA-2 scaffolds privileged DNA repair compartments that promote crossover-factor accumulation and protect crossover intermediates until completion of repair, thereby ensuring that crossover-designated sites reliably mature into crossovers.

developmental biology↗

bioRxiv2023

Caenorhabditis elegans germ granules are present in distinct configurations that differentially associate with RNAi-targeted RNAs

RNA silencing pathways are complex, highly conserved, and perform widespread, critical regulatory roles. In C. elegans germlines, RNA surveillance occurs through a series of perinuclear germ granule compartments--P granules, Z granules, SIMR foci, and Mutator foci--multiple of which form via phase separation and exhibit liquid-like properties. The functions of individual proteins within germ granules are well-studied, but the spatial organization, physical interaction, and coordination of biomolecule exchange between compartments within germ granule "nuage" is less understood. Here we find that key proteins are sufficient for compartment separation, and that the boundary between compartments can be reestablished after perturbation. Using super-resolution microscopy, we discover a toroidal P granule morphology which encircles the other germ granule compartments in a consistent exterior-to-interior spatial organization. Combined with findings that nuclear pores primarily interact with P granules, this nuage compa rtment organization has broad implications for the trajectory of an RNA as it exits the nucleus and enters small RNA pathway compartments. Furthermore, we quantify the stoichiometric relationships between germ granule compartments and RNA to reveal discrete populations of nuage that differentially associate with RNAi-targeted transcripts, possibly suggesting functional differences between nuage configurations. Together, our work creates a more spatially and compositionally accurate model of C. elegans nuage which informs the conceptualization of RNA silencing through different germ granule compartments.

cell biology↗

bioRxiv2020

Mutator foci are regulated by developmental stage, RNA, and the germline cell cycle in Caenorhabditis elegans

RNA interference is a crucial gene regulatory mechanism in Caenorhabditis elegans. Phase-separated perinuclear germline compartments called Mutator foci are a key element of RNAi, ensuring robust gene silencing and transgenerational epigenetic inheritance. Despite their importance, Mutator foci regulation is not well understood, and observations of Mutator foci have been largely limited to adult hermaphrodite germlines. Here we reveal that punctate Mutator foci arise in the progenitor germ cells of early embryos and persist throughout all larval stages. They are additionally present throughout the male germline and in the cytoplasm of post-meiotic spermatids, suggestive of a role in paternal epigenetic inheritance. In the adult germline, transcriptional inhibition results in a pachytene-specific loss of Mutator foci, indicating that Mutator foci are partially reliant on RNA for their stability. Finally, we demonstrate that Mutator foci intensity is modulated by the stage of the germline cell cycle and specifically, that Mutator foci are brightest and most robust in the mitotic cells, transition zone, and late pachytene of adult germlines. Thus, our data defines several new factors that modulate Mutator foci morphology which may ultimately have implications for efficacy of RNAi in certain cell stages or environments.

genetics↗