Authors
Zagoskin, M. V., Kang, Y., Davis, R. E., Wang, J.
Abstract
Programmed DNA elimination (PDE) selectively removes portions of the genome during development, deviating from the genome constancy rule. Our understanding of PDE mechanisms, including the involvement of small RNAs and transposases, is mainly based on studies in the single-cell ciliates, whereas in metazoans, the PDE mechanisms remain largely unknown. In the parasitic nematode Ascaris, PDE removes and remodels all germline chromosome ends, splits fused chromosomes into somatic chromosomes, leading to dramatic karyotype changes. To probe the possible involvement of small RNAs in Ascaris PDE, we identified two Argonautes, AsWAGO-2 and AsWAGO-3, associated with PDE. Using cellular fractionation followed by nuclease-treated immunoprecipitation, we characterized WAGO-associated small RNAs (siRNAs) and their targets in chromatin, nucleoplasm, and cytoplasm. We found that AsWAGO-3 is enriched on eliminated chromatin, with its associated siRNAs mostly targeting genes. However, a subset of AsWAGO-3 siRNAs targets repeats in the eliminated regions specifically located in the middle of chromosomes that originated from the ends of ancestral chromosomes. In contrast, AsWAGO-2 transiently stains the retained chromosomes during elimination mitoses, and the associated siRNAs are enriched in the retained regions only in the chromatin fraction. Overall, our data established a link between WAGOs and Ascaris PDE, demonstrating the flexibility of small RNA pathways that selectively distinguish retained and eliminated DNA. We suggest that some of the targeting may be a response to the karyotype changes associated with chromosome fusion and PDE.
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bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Oct 2025.
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