Evidence map›Paper›PMID 34428467›Full record

ArticleCurrent biology : CB2021

piRNAs coordinate poly(UG) tailing to prevent aberrant and perpetual gene silencing.

Aditi Shukla, Roberto Perales, Scott Kennedy

Open access · greenAbstract read
In one paragraph

Article in Current biology : CB, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 49 citations in OpenAlex.

  1. bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. RNA helicase unravels the secrets of germ granules.Nature structural & molecular biology · 2025
    Article
  7. Article
  8. Intraspecific variation in the duration of epigenetic inheritance.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Solution Structure of Poly(UG) RNA.Journal of molecular biology · 2023
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Aditi ShuklaDepartment of Genetics, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Roberto PeralesDepartment of Genetics, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA; Shape Therapeutics, Seattle, WA 98109, USA.
Scott KennedyDepartment of Genetics, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA. Electronic address: kennedy@genetics.med.harvard.edu.
Harvard University · US

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
Small Regulatory RNA Functions In The NucleusR01GM088289 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI KENNEDY, SCOTT G · 2009 to 2022
$4.4M
Identification and Characterization of Systems that Limit Transgenerational Epigenetic Inheritance (TEI)F32GM120919 · NIGMS · HARVARD MEDICAL SCHOOL · PI PERALES, ROBERTO · 2017 to 2017
$63k
NIGMS NIH HHS F32 GM120919NIGMS NIH HHS R01 GM088289NIH HHS P40 OD010440
6 · The paper itself

Abstract

Noncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of such RNA-directed TEI is the inheritance of gene-silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite the self-perpetuating nature of pUG RNA/siRNA cycling, RNAi inheritance is finite, suggesting that systems likely exist to prevent indefinite RNAi-triggered gene silencing. Here we show that, in the absence of Piwi-interacting RNAs (piRNAs), an animal-specific class of small noncoding RNA, RNAi-based gene silencing can become essentially permanent, lasting at near 100% penetrance for more than 5 years and hundreds of generations. This perpetual gene silencing is mediated by continuous pUG RNA/siRNA cycling. Further, we find that piRNAs coordinate endogenous RNAi pathways to prevent germline-expressed genes, which are not normally subjected to TEI, from entering a state of continual and irreversible epigenetic silencing also mediated by continuous maintenance of pUG RNA/siRNA cycling. Together, our results show that one function of C. elegans piRNAs is to insulate germline-expressed genes from aberrant and runaway inactivation by the pUG RNA/siRNA epigenetic inheritance system.

Indexed as

Caenorhabditis elegansCaenorhabditis elegans ProteinsAnimalsArgonaute ProteinsGene SilencingRNA, Double-StrandedRNA InterferenceRNA, MessengerRNA, Small InterferingArgonaute ProteinsCaenorhabditis elegans ProteinsRNA, Double-StrandedRNA, MessengerRNA, Small InterferingArgonauteepigeneticsgerm granulespiRNAsRNAiRNA modificationssiRNAssmall RNAstransgenerational inheritance

Identifiers

PMID34428467
PMCPMC9067611
OpenAlexW3193516527

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.