Evidence map›Paper›PMID 24401661›Full record

ArticleGenome biology2014

Global target mRNA specification and regulation by the RNA-binding protein ZFP36.

Neelanjan Mukherjee, Nicholas C Jacobs, Markus Hafner, Elizabeth A Kennington, Jeffrey D Nusbaum, Thomas Tuschl, Perry J Blackshear, Uwe Ohler

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
8.1field-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

110 citing papers in PubMed, 162 citations in OpenAlex.

  1. Article
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  6. Spatial multiomics profiling reveals ZFP36-mediated immunometabolic reprogramming in bladder cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Review
  9. Meta-unstable mRNAs in activated CD8Nature communications · 2026
    Article
  10. Review
  11. Beyond transcription: RNA-binding proteins steering angiogenesis.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  12. Article
  13. Article
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  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Post-transcriptional checkpoints in autoimmunity.Nature reviews. Rheumatology · 2023
    Review

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

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

8 authors at 4 institutions in 2 countries.

Neelanjan Mukherjee
Nicholas C Jacobs
Markus Hafner
Elizabeth A Kennington
Jeffrey D Nusbaum
Thomas Tuschl
Perry J Blackshear
Uwe Ohler
Max Delbrück Center · DEHoward Hughes Medical Institute · USNational Institute of Environmental Health Sciences · USRockefeller University · US

Funding

TTP and related proteins in the regulation of gene expressionZIAES090080 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BLACKSHEAR, PERRY J · 2009 to 2025
$52.6M
The role of AU-rich element binding proteins in shaping target mRNA expressionZIAAR041200 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI HAFNER, MARKUS · 2014 to 2023
$5.1M
Posttranscriptional regulation by mRNA-binding shuttling and transport proteinsR01GM104962 · NIGMS · ROCKEFELLER UNIVERSITY · PI OHLER, UWE, PATEL, DINSHAW J · 2012 to 2016
$4.4M
Intramural NIH HHSNIGMS NIH HHS R01 GM104962NIGMS NIH HHS R01-GM104962
6 · The paper itself

Abstract

backgroundZFP36, also known as tristetraprolin or TTP, and ELAVL1, also known as HuR, are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embryonic kidney cells, and examined the combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1.

resultsTargets bound and negatively regulated by ZFP36 include transcripts encoding proteins necessary for immune function and cancer, and transcripts encoding other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance upon ZFP36 overexpression independent of effects from confounding features. Genes with increased mRNA half-lives in ZFP36 knockout versus wild-type mouse cells were significantly enriched for our human ZFP36 targets. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes, and found that ZFP36 degrades transcripts through specific AU-rich sequences, representing a subset of the U-rich sequences ELAVL1 interacts with to stabilize transcripts.

conclusionsZFP36-RNA target specificities in vivo are quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to unravel in vivo combinatorial regulation by RNA-binding proteins.

Indexed as

Gene Expression RegulationComputational BiologyELAV-Like Protein 1HEK293 CellsHumansImmunoprecipitationRNA-Binding ProteinsRNA, MessengerSequence Analysis, RNASoftwareTristetraprolinELAVL1 protein, humanELAV-Like Protein 1RNA-Binding ProteinsRNA, MessengerTristetraprolinZFP36 protein, human

Identifiers

PMID24401661
PMCPMC4053807
OpenAlexW2158953547

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.