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假尿苷引导种系小RNA转运和表观遗传继承。

Pseudouridine guides germline small RNA transport and epigenetic inheritance.

作者信息

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

机构信息

Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

Department of Biochemistry, University of Otago, Dunedin, New Zealand.

出版信息

Nat Struct Mol Biol. 2025 Feb;32(2):277-286. doi: 10.1038/s41594-024-01392-6. Epub 2024 Sep 6.

DOI:10.1038/s41594-024-01392-6
PMID:39242979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11832342/
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.

摘要

植物和动物中的发育表观遗传修饰在配子形成过程中大多会被重置，但有些会从生殖系遗传下来。小RNA引导这些表观遗传修饰，但植物和动物中如何区分遗传的小RNA尚不清楚。假尿苷（Ψ）是最丰富的RNA修饰，但尚未在小RNA中进行探索。在这里，我们开发了检测短RNA序列中Ψ的方法，证明其存在于小鼠和拟南芥的 microRNA 中。生殖系小RNA，即拟南芥花粉中的表观遗传激活小干扰RNA（easiRNA）和小鼠睾丸中的 Piwi 相互作用RNA，富含Ψ。在花粉中，假尿苷化的 easiRNA 从营养核运输到精细胞，而 Exportin-t 的植物同源物 PAUSED/HEN5（PSD）在遗传上与Ψ相互作用，并且是这种运输所必需的。我们进一步表明，Exportin-t 是三倍体阻断所必需的：小RNA剂量依赖性种子致死性，它从花粉表观遗传继承。因此，Ψ在标记生殖系中遗传的小RNA方面具有保守作用。

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