Herridge, Rowan P, Dolata, Jakub, Migliori, Valentina, de Santis Alves, Cristiane, Borges, Filipe, Schorn, Andrea J, van Ex, Frédéric, Lin, Ann, Bajczyk, Mateusz, Parent, Jean-Sebastien, Leonardi, Tommaso, Hendrick, Alan, Kouzarides, Tony, Martienssen, Robert A (September 2024) Pseudouridine guides germline small RNA transport and epigenetic inheritance. Nature Structural & Molecular Biology. ISSN 1545-9993 (Public Dataset)
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Abstract
Developmental epigenetic modifications in plants and animals are mostly reset during gamete formation but some are inherited from the germline. Small RNAs guide these epigenetic modifications but how inherited small RNAs are distinguished in plants and animals is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs. Germline small RNAs, namely epigenetically activated small interfering RNAs (easiRNAs) in Arabidopsis pollen and Piwi-interacting RNAs in mouse testes, are enriched for Ψ. In pollen, pseudouridylated easiRNAs are transported to sperm cells from the vegetative nucleus, and PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for this transport. We further show that Exportin-t is required for the triploid block: small RNA dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.
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