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Resources » Paper

Shukla A et al. (2020) Nature "poly(UG)-tailed RNAs in genome protection and epigenetic inheritance."

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  • Comments on Shukla A et al. (2020) Nature "poly(UG)-tailed RNAs in genome protection and epigenetic inheritance." (0)

  • Overview

    PMID:
    32499657
    DOI:
    10.1038/s41586-020-2323-8
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00059776

    Shukla A, Yan J, Pagano DJ, Dodson AE, Fei Y, Gorham J, Seidman JG, Wickens M, & Kennedy S (2020). poly(UG)-tailed RNAs in genome protection and epigenetic inheritance. Nature. doi:10.1038/s41586-020-2323-8

    Mobile genetic elements threaten genome integrity in all organisms. RDE-3 (also known as MUT-2) is a ribonucleotidyltransferase that is required for transposon silencing and RNA interference in Caenorhabditis elegans<sup>1-4</sup>. When tethered to RNAs in heterologous expression systems, RDE-3 can add long stretches of alternating non-templated uridine (U) and guanosine (G) ribonucleotides to the 3' termini of these RNAs (designated poly(UG) or pUG tails)<sup>5</sup>. Here we show that, in its natural context in C. elegans, RDE-3 adds pUG tails to targets of RNA interference, as well as to transposon RNAs. RNA fragments attached to pUG tails with more than 16 perfectly alternating 3' U and G nucleotides become gene-silencing agents. pUG tails promote gene silencing by recruiting RNA-dependent RNA polymerases, which use pUG-tailed RNAs (pUG RNAs) as templates to synthesize small interfering RNAs (siRNAs). Our results show that cycles of pUG RNA-templated siRNA synthesis and siRNA-directed pUG RNA biogenesis underlie double-stranded-RNA-directed transgenerational epigenetic inheritance in the C. elegans germline. We speculate that this pUG RNA-siRNA silencing loop enables parents to inoculate progeny against the expression of unwanted or parasitic genetic elements.

    Authors: Shukla A, Yan J, Pagano DJ, Dodson AE, Fei Y, Gorham J, Seidman JG, Wickens M, Kennedy S


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