Argonautes and small RNAs associated with nematode programmed DNA elimination

Abstract

Programmed DNA elimination (PDE) selectively removes DNA in pre-somatic cells to form the somatic genome during development. Our mechanistic understanding of PDE is mainly based on studies in the single-cell ciliates, where small RNAs and transposases are involved. In contrast, the mechanism(s) of metazoan PDE remains largely unknown. In the parasitic nematode Ascaris, PDE removes and remodels all germline chromosome ends and partitions fused germline chromosomes into somatic chromosomes, resulting in dramatic karyotype changes. Here, we identified two Ascaris Argonautes, AsWAGO-2 and AsWAGO-3, associated with retained or eliminated chromosome regions, respectively, during PDE mitoses. AsWAGO-3 siRNAs target primarily genes. However, a subset of AsWAGO-3 siRNAs targets repeats within the eliminated regions and located in the middle of chromosomes. These chromosome regions are derived from the fusion of the ends of ancestral chromosomes. In contrast, AsWAGO-2 and its associated siRNAs are transiently enriched on retained chromosomes during elimination mitoses. Overall, our data reveal a link between Ascaris WAGOs, their siRNAs, and PDE, identifying small RNA pathways that selectively distinguish retained and eliminated DNA. We suggest that AsWAGO-3 associated small RNAs targeting the interior of select chromosomes may be a response to the fusions of germline chromosomes.