Evidence map›Paper›PMID 14664697›Full record

ArticleThe Biochemical journal2004

Characterization of a cis-acting regulatory element in the protein-coding region of human dihydrofolate reductase mRNA.

Ningwen Tai, John C Schmitz, Tian-min Chen, Edward Chu

Open access · bronzeAbstract read
In one paragraph

Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

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  14. miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit.Clinical cancer research : an official journal of the American Association for Cancer Research · 2008
    Article
  15. 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 at 1 institution in 1 country.

Ningwen TaiDepartment of Medicine and Pharmacology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
John C Schmitz
Tian-min Chen
Edward Chu
Yale Cancer Center · US

Funding

Molecular Regulation of Translational RegulationR01CA082897 · NCI · YALE UNIVERSITY · PI CHU, EDWARD · 1999 to 2008
$1.7M
MOLECULAR BASIS FOR TS TRANSLATIONAL REGULATIONR01CA075712 · NCI · YALE UNIVERSITY · PI CHU, EDWARD · 1997 to 2005
$1.2M
NCI NIH HHS CA75712NCI NIH HHS CA82897
6 · The paper itself

Abstract

Previous studies have shown that human DHFR (dihydrofolate reductase), in addition to its critical role in DNA biosynthesis, functions as an RNA-binding protein. The interaction between DHFR and its own mRNA results in translational repression. In this study, we characterized the cis-acting elements on human DHFR mRNA that are required for the DHFR mRNA-DHFR protein interaction. Using a series of gel-shift and nitrocellulose filter-binding assays, a 164 nt RNA sequence, corresponding to nt 401-564, was identified within the coding region that binds to DHFR protein with an affinity similar to that of full-length DHFR mRNA. To document in vivo biological activity, various DHFR sequences contained within the coding region were cloned on to the 5' end of a luciferase reporter plasmid, and transient transfection experiments were performed using human colon cancer RKO cells. In cells transfected with p644/DHFR:401-564, luciferase activity was decreased by 50% when compared with cells transfected with the p644 plasmid alone. Luciferase mRNA levels were identical under each of these conditions, as determined by Northern-blot analysis. In cells transfected with p644/DHFR:401-564, luciferase activity was restored to almost 100% of control when cells were treated with the antifolate analogue methotrexate or with a short-interfering RNA targeting DHFR mRNA. These findings provide evidence that the DHFR 401-564 sequence is a DHFR-response element. In vitro and in vivo studies further localized this cis-element to an 82 nt sequence corresponding to nt 401-482. This work provides new insights into critical elements that mediate RNA-protein interactions.

Indexed as

Protein BiosynthesisRegulatory Sequences, Ribonucleic AcidResponse ElementsBinding SitesCell Line, TumorExonsGene Expression RegulationHumansLuciferasesRNA, MessengerTetrahydrofolate DehydrogenaseLuciferasesRegulatory Sequences, Ribonucleic AcidRNA, MessengerTetrahydrofolate Dehydrogenase

Identifiers

PMID14664697
PMCPMC1224025
OpenAlexW1994119394

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.