Evidence map›Paper›PMID 23415457›Full record

ArticleCell2013

Stalled spliceosomes are a signal for RNAi-mediated genome defense.

Phillip A Dumesic, Prashanthi Natarajan, Changbin Chen, Ines A Drinnenberg, Benjamin J Schiller, James Thompson, James J Moresco, John R Yates, David P Bartel, Hiten D Madhani

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
8.7field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 188 citations in OpenAlex.

  1. Article
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  6. Article
  7. Article
  8. Review
  9. Article
  10. PhpCNature communications · 2025
    Article
  11. Review
  12. Distinct evolutionary trajectories following loss of RNA interference inProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Review
  14. Distinct evolutionary trajectories following loss of RNA interference inbioRxiv : the preprint server for biology · 2024
    Article
  15. A Chimeric ORF Fusion Phenotypic Reporter forJournal of fungi (Basel, Switzerland) · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Comparative genomics ofbioRxiv : the preprint server for biology · 2024
    Article
  20. Gene Silencing via RNA Interference in Cryptococcus.Methods in molecular biology (Clifton, N.J.) · 2024
    Article

52 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Phillip A DumesicDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Prashanthi Natarajan
Changbin Chen
Ines A Drinnenberg
Benjamin J Schiller
James Thompson
James J Moresco
John R Yates
David P Bartel
Hiten D Madhani
University of California, San Francisco · USScripps Research Institute · USWhitehead Institute for Biomedical Research · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
ZDS2P REGULATES SWE1P-DEPENDENT POLARIZED CELL GROWTH IN S CEREVISIAEP41RR011823 · NCRR · UNIVERSITY OF WASHINGTON · PI DAVIS, TRACY · 1996 to 2011
$24.7M
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
Mechanisms of Gene SilencingR01GM071801 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Hiten D Madhani · 2005 to 2026
$7.1M
Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
Genetic Regulation of the Response to Dietary RestrictionR01AG027463 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI DILLIN, ANDREW G · 2008 to 2012
$2.4M
RNA Conformation and CatalysisR37GM061835 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI BARTEL, DAVID P · 2011 to 2016
$2.3M
NCRR NIH HHS 5P41RR011823-17NCRR NIH HHS P41 RR011823NIAID NIH HHS T32 AI060537NIA NIH HHS R01 AG027463NIA NIH HHS R01AG027463-04NIGMS NIH HHS 8 P41 GM103533-17NIGMS NIH HHS P41 GM103533NIGMS NIH HHS R01 GM071801NIGMS NIH HHS R37 GM061835NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

Using the yeast Cryptococcus neoformans, we describe a mechanism by which transposons are initially targeted for RNAi-mediated genome defense. We show that intron-containing mRNA precursors template siRNA synthesis. We identify a Spliceosome-Coupled And Nuclear RNAi (SCANR) complex required for siRNA synthesis and demonstrate that it physically associates with the spliceosome. We find that RNAi target transcripts are distinguished by suboptimal introns and abnormally high occupancy on spliceosomes. Functional investigations demonstrate that the stalling of mRNA precursors on spliceosomes is required for siRNA accumulation. Lariat debranching enzyme is also necessary for siRNA production, suggesting a requirement for processing of stalled splicing intermediates. We propose that recognition of mRNA precursors by the SCANR complex is in kinetic competition with splicing, thereby promoting siRNA production from transposon transcripts stalled on spliceosomes. Disparity in the strength of expression signals encoded by transposons versus host genes offers an avenue for the evolution of genome defense.

Indexed as

DNA Transposable ElementsRNA InterferenceCryptococcus neoformansGenome, FungalIntronsKineticsRNA-Dependent RNA PolymeraseRNA, MessengerRNA, NuclearRNA, Small InterferingSpliceosomesDNA Transposable ElementsRNA-Dependent RNA PolymeraseRNA, MessengerRNA, NuclearRNA, Small Interfering

Identifiers

PMID23415457
PMCPMC3645481
OpenAlexW1987112627

What OpenQuestion holds

Textmetadata
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.