Evidence map›Paper›PMID 19939970›Full record

ArticleRNA (New York, N.Y.)2010

Multiple determinants within iron-responsive elements dictate iron regulatory protein binding and regulatory hierarchy.

Jeremy B Goforth, Sheila A Anderson, Christopher P Nizzi, Richard S Eisenstein

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

35 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Iron-responsive-like elements and neurodegenerative ferroptosis.Learning & memory (Cold Spring Harbor, N.Y.) · 2020
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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 at 1 institution in 1 country.

Jeremy B GoforthDepartment of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Sheila A Anderson
Christopher P Nizzi
Richard S Eisenstein
University of Wisconsin–Madison · US

Funding

TRAINING IN NUTRITIONT32DK007665 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI GUY E GROBLEWSKI, Chi- Liang Eric Yen · 1993 to 2026
$9.2M
Biological Functions of Iron Responsive ElementsR01DK066600 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI EISENSTEIN, RICHARD S. · 2005 to 2017
$3.4M
Biological Functions of Iron Responsive ElementsR56DK066600 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI EISENSTEIN, RICHARD S. · 2012 to 2012
$90k
NIDDK NIH HHS R01 DK066600NIDDK NIH HHS R01 DK 66600NIDDK NIH HHS R56 DK066600NIDDK NIH HHS T32 DK 007665NIDDK NIH HHS T32 DK007665
6 · The paper itself

Abstract

Iron regulatory proteins (IRPs) are iron-regulated RNA binding proteins that, along with iron-responsive elements (IREs), control the translation of a diverse set of mRNA with 5' IRE. Dysregulation of IRP action causes disease with etiology that may reflect differential control of IRE-containing mRNA. IREs are defined by a conserved stem-loop structure including a midstem bulge at C8 and a terminal CAGUGH sequence that forms an AGU pseudo-triloop and N19 bulge. C8 and the pseudo-triloop nucleotides make the majority of the 22 identified bonds with IRP1. We show that IRP1 binds 5' IREs in a hierarchy extending over a ninefold range of affinities that encompasses changes in IRE binding affinity observed with human L-ferritin IRE mutants. The limits of this IRE binding hierarchy are predicted to arise due to small differences in binding energy (e.g., equivalent to one H-bond). We demonstrate that multiple regions of the IRE stem not predicted to contact IRP1 help establish the binding hierarchy with the sequence and structure of the C8 region displaying a major role. In contrast, base-pairing and stacking in the upper stem region proximal to the terminal loop had a minor role. Unexpectedly, an N20 bulge compensated for the lack of an N19 bulge, suggesting the existence of novel IREs. Taken together, we suggest that a regulatory binding hierarchy is established through the impact of the IRE stem on the strength, not the number, of bonds between C8 or pseudo-triloop nucleotides and IRP1 or through their impact on an induced fit mechanism of binding.

Indexed as

Nucleic Acid ConformationAnimalsApoferritinsBase SequenceHumansIron Regulatory Protein 1Iron-Regulatory ProteinsMetabolic Networks and PathwaysModels, MolecularMolecular Sequence DataPhylogenyProtein BindingRabbitsResponse ElementsRNA-Binding ProteinsSaccharomyces cerevisiaeApoferritinsIron Regulatory Protein 1Iron-Regulatory ProteinsRNA-Binding Proteins

Identifiers

PMID19939970
PMCPMC2802025
OpenAlexW2104189321

What OpenQuestion holds

Textmetadata
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.