Evidence map›Paper›PMID 22810205›Full record

ArticleNucleic acids research2012

Right- and left-loop short shRNAs have distinct and unusual mechanisms of gene silencing.

Anne Dallas, Heini Ilves, Qing Ge, Pavan Kumar, Joshua Shorenstein, Sergei A Kazakov, Trinna L Cuellar, Michael T McManus, Mark A Behlke, Brian H Johnston

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 43 citations in OpenAlex.

  1. Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  2. Article
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  11. Review
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  13. Review
  14. Article
  15. Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.Molecular therapy. Methods & clinical development · 2017
    Article
  16. Article
  17. Development of Novel Small Hairpin RNAs That do not Require Processing by Dicer or AGO2.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Article
  18. Article
  19. Alleviation of off-target effects from vector-encoded shRNAs via codelivered RNA decoys.Proceedings of the National Academy of Sciences of the United States of America · 2015
    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

10 authors at 3 institutions in 1 country.

Anne DallasSomaGenics, Inc., 2161 Delaware Avenue, Santa Cruz, CA 95060, USA.
Heini Ilves
Qing Ge
Pavan Kumar
Joshua Shorenstein
Sergei A Kazakov
Trinna L Cuellar
Michael T McManus
Mark A Behlke
Brian H Johnston
SomaGenics (United States) · USStanford University · USIntegrated DNA Technologies (United States) · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
Inhibition of hepatitis C by RNA-based therapeuticsR44AI056611 · NIAID · SOMAGENICS, INC. · PI JOHNSTON, BRIAN H. · 2005 to 2007
$3.1M
Chemical Stabilization of shRNAs and their development as hepatitis C drugsR44AI074256 · NIAID · SOMAGENICS, INC. · PI JOHNSTON, BRIAN H. · 2011 to 2013
$2.8M
New Frontiers for Small RNA TherapiesR01GM080783 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCMANUS, MICHAEL T · 2007 to 2011
$1.5M
An RNAi Trojan Horse for treatment of hepatitis C.R43AI074214 · NIAID · SOMAGENICS, INC. · PI JOHNSTON, BRIAN H. · 2008 to 2009
$596k
NIAID NIH HHS R43 AI074214NIAID NIH HHS R43AI074214NIAID NIH HHS R44 AI056611NIAID NIH HHS R44AI056611NIAID NIH HHS R44 AI074256NIAID NIH HHS R44AI074256NIDDK NIH HHS DK063720NIDDK NIH HHS P30 DK063720NIGMS NIH HHS R01 GM080783NIGMS NIH HHS R01GM80783
6 · The paper itself

Abstract

Small hairpin RNAs (shRNAs) having duplex lengths of 25-29 bp are normally processed by Dicer into short interfering RNAs (siRNAs) before incorporation into the RNA-induced silencing complex (RISC). However, shRNAs of ≤ 19 bp [short shRNAs (sshRNAs)] are too short for Dicer to excise their loops, raising questions about their mechanism of action. sshRNAs are designated as L-type or R-type according to whether the loop is positioned 3' or 5' to the guide sequence, respectively. Using nucleotide modifications that inhibit RNA cleavage, we show that R- but not L-sshRNAs require loop cleavage for optimum activity. Passenger-arm slicing was found to be important for optimal functioning of L-sshRNAs but much less important for R-sshRNAs that have a cleavable loop. R-sshRNAs could be immunoprecipitated by antibodies to Argonaute-1 (Ago1); complexes with Ago1 contained both intact and loop-cleaved sshRNAs. In contrast, L-sshRNAs were immunoprecipitated with either Ago1 or Ago2 and were predominantly sliced in the passenger arm of the hairpin. However, 'pre-sliced' L-sshRNAs were inactive. We conclude that active L-sshRNAs depend on slicing of the passenger arm to facilitate opening of the duplex, whereas R-sshRNAs primarily act via loop cleavage to generate a 5'-phosphate at the 5'-end of the guide strand.

Indexed as

RNA InterferenceArgonaute ProteinsCell LineHumansImmunoprecipitationMicroRNAsRibonuclease IIIRNA CleavageRNA-Induced Silencing ComplexRNA PrecursorsRNA, Small InterferingAGO2 protein, humanArgonaute ProteinsMicroRNAsRibonuclease IIIRNA-Induced Silencing ComplexRNA PrecursorsRNA, Small Interfering

Identifiers

PMID22810205
PMCPMC3467060
OpenAlexW2154212814

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.