Evidence map›Paper›PMID 22140441›Full record

ArticlePloS one2011

A systematic analysis of the 3'UTR of HNF4A mRNA reveals an interplay of regulatory elements including miRNA target sites.

Andrea Wirsing, Sabine Senkel, Ludger Klein-Hitpass, Gerhart U Ryffel

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

25 citing papers in PubMed, 38 citations in OpenAlex.

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  9. Transcriptional Regulation of CYP2D6 Expression.Drug metabolism and disposition: the biological fate of chemicals · 2017
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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 2 institutions in 1 country.

Andrea WirsingInstitut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
Sabine Senkel
Ludger Klein-Hitpass
Gerhart U Ryffel
Essen University Hospital · DEUniversity of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysfunction of hepatocyte nuclear factor 4α (HNF4α) has been linked to maturity onset diabetes of the young (MODY1), diabetes type II and possibly to renal cell carcinoma (RCC). Whereas diabetes causing mutations are well known, there are no HNF4A mutations found in RCC. Since so far analyses have been constricted to the promoter and open reading frame of HNF4A, we performed a systematic analysis of the human HNF4A 3'UTR. We identified a short (1724 nt) and long (3180 nt) 3'UTR that are much longer than the open reading frame and conferred a repressive effect in luciferase reporter assays in HEK293 and INS-1 cells. By dissecting the 3'UTR into several pieces, we located two distinct elements of about 400 nt conferring a highly repressive effect. These negative elements A and B are counteracted by a balancer element of 39 nt located within the 5' end of the HNF4A 3'UTR. Dicer knock-down experiments implied that the HNF4A 3'UTR is regulated by miRNAs. More detailed analysis showed that miR-34a and miR-21 both overexpressed in RCC cooperate in downregulation of the HNF4A mRNA. One of the identified miR-34a binding sites is destroyed by SNP rs11574744. The identification of several regulatory elements within the HNF4A 3'UTR justifies the analysis of the 3'UTR sequence to explore the dysfunction of HNF4α in diabetes and RCC.

Indexed as

3' Untranslated RegionsBase SequenceBinding SitesGene Expression RegulationGene Knockdown TechniquesGenes, ReporterHEK293 CellsHepatocyte Nuclear Factor 4HumansMicroRNAsMolecular Sequence DataPolyadenylationPolymorphism, Single NucleotideRegulatory Sequences, Nucleic AcidRibonuclease IIIRNA, Messenger3' Untranslated RegionsHepatocyte Nuclear Factor 4HNF4A protein, humanMicroRNAsMIRN21 microRNA, humanMIRN34 microRNA, humanRibonuclease IIIRNA, Messenger

Identifiers

PMID22140441
PMCPMC3227676
OpenAlexW2039781333

What OpenQuestion holds

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LicenceCC BY
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.