poly(UG)-tailed RNAs in genome protection and epigenetic inheritance

Aditi Shukla, Jenny Yan, Daniel J. Pagano, Anne E. Dodson, Yuhan Fei, Josh Gorham, J. G. Seidman, Marvin Wickens and Scott Kennedy ()
Additional contact information
Aditi Shukla: Blavatnik Institute at Harvard Medical School
Jenny Yan: Blavatnik Institute at Harvard Medical School
Daniel J. Pagano: Blavatnik Institute at Harvard Medical School
Anne E. Dodson: Blavatnik Institute at Harvard Medical School
Yuhan Fei: Blavatnik Institute at Harvard Medical School
Josh Gorham: Blavatnik Institute at Harvard Medical School
J. G. Seidman: Blavatnik Institute at Harvard Medical School
Marvin Wickens: University of Wisconsin–Madison
Scott Kennedy: Blavatnik Institute at Harvard Medical School

Nature, 2020, vol. 582, issue 7811, 283-288

Abstract: Abstract 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 elegans1–4. 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)5. 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2323-8 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:582:y:2020:i:7811:d:10.1038_s41586-020-2323-8

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2323-8

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().