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Pseudouridine guides small RNA transport and inheritance via Exportin-t

ABSTRACT: Pseudouridine (Ψ) is an isomer of uridine found in ribosomal, transfer and other structural RNAs as well as in some mRNAs and non-coding RNAs, but is difficult to detect in short RNA sequences. Using modified techniques we found Ψ in microRNAs (miRNAs) and their precursors from mammalian and plant cells, primarily at the 5ʹ terminus of the mature miRNA. Small RNAs targeting transposons in reproductive cells (piRNA in testis and easiRNA in pollen) were highly enriched for Ψ, indicating a potential role in epigenetic inheritance. In pollen, pseudouridylated small RNAs were produced by RNA polymerase IV and were localized to sperm cells, as were miRNAs with terminal Ψ. We show that pseudouridylated easiRNAs from pollen contribute to imprinting and the triploid block (chromosome dosage-dependent epigenetic lethality) via the activity of PAUSED/HEN5, the plant homolog of Exportin-t. Exportin-t is required for nuclear export of pseudouridylated tRNA, and we found that PSD is required for cell-cell transport of small RNA in the germline.

ORGANISM(S): Mus musculus

PROVIDER: GSE229986 | GEO | 2023/08/07

REPOSITORIES: GEO

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Pseudouridine guides germline small RNA transport and epigenetic inheritance.

Project description:Epigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation. In C. elegans, these inherited small RNAs have poly (UG) tails, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we developed novel assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs and their precursors. We also detected substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) in Arabidopsis pollen, and PIWI-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are produced by RNA polymerase IV and localized to sperm cells. We found that PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ synthase and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that PSD is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. We propose that Ψ has a conserved role in marking inherited small RNAs in the germline.

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Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [RNA-seq]

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