Evidence map›Paper›PMID 23141544›Full record

ArticleCell2012

Protection from feed-forward amplification in an amplified RNAi mechanism.

Julia Pak, Jay Mahesh Maniar, Cecilia Cabral Mello, Andrew Fire

Abstract read
In one paragraph

Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
–field-weighted citation impact
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

54 citing papers in PubMed.

  1. Article
  2. Article
  3. Intraspecific variation in the duration of epigenetic inheritance.bioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Heritable Epigenetic Changes Alter Transgenerational Waveforms Maintained by Cycling Stores of Information.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020
    Article
  16. Multigenerational Regulation of theAnnual review of genetics · 2019
    Review
  17. Review
  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

4 authors.

Julia PakDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jay Mahesh ManiarDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cecilia Cabral MelloDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Andrew FireDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: afire@stanford.edu.

Funding

GENE REGULATION DURING EARLY DEVELOPMENT OF C. ELEGANSR01GM037706 · NIGMS · STANFORD UNIVERSITY · PI FIRE, ANDREW Z. · 1987 to 2018
$11.0M
TUMOR BIOLOGYT32CA009151 · NCI · STANFORD UNIVERSITY · PI CLEARY, MICHAEL L · 1985 to 2014
$5.5M
NCI NIH HHS T32 CA009151NIGMS NIH HHS R01 GM037706NIGMS NIH HHS R01GM37706
6 · The paper itself

Abstract

The effectiveness of RNA interference (RNAi) in many organisms is potentiated through the signal-amplifying activity of a targeted RNA-directed RNA polymerase (RdRP) system that can convert a small population of exogenously-encountered dsRNA fragments into an abundant internal pool of small interfering RNA (siRNA). As for any biological amplification system, we expect an underlying architecture that will limit the ability of a randomly encountered trigger to produce an uncontrolled and self-escalating response. Investigating such limits in Caenorhabditis elegans, we find that feed-forward amplification is limited by biosynthetic and structural distinctions at the RNA level between (1) triggers that can produce amplification and (2) siRNA products of the amplification reaction. By assuring that initial (primary) siRNAs can act as triggers but not templates for activation, and that the resulting (secondary) siRNAs can enforce gene silencing on additional targets without unbridled trigger amplification, the system achieves substantial but fundamentally limited signal amplification.

Indexed as

RNA InterferenceAnimalsBase SequenceCaenorhabditis elegansCaenorhabditis elegans ProteinsGene SilencingMolecular Sequence DataRNA-Binding ProteinsRNA-Dependent RNA PolymeraseRNA, Double-StrandedRNA, Small InterferingCaenorhabditis elegans Proteinsrde-1 protein, C elegansRDE-4 protein, C elegansRNA-Binding ProteinsRNA-Dependent RNA PolymeraseRNA, Double-StrandedRNA, Small InterferingSEL-1 protein, C elegans

Identifiers

PMID23141544
PMCPMC3499135

What OpenQuestion holds

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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.