Evidence map›Paper›PMID 19141871›Full record

ArticleJournal of lipid research2009

Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements.

Hai Li, Wei Chen, Yue Zhou, Parveen Abidi, Orr Sharpe, William H Robinson, Fredric B Kraemer, Jingwen Liu

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 91 citations in OpenAlex.

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  2. Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin.Arteriosclerosis, thrombosis, and vascular biology · 2010 · on this map
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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

8 authors at 1 institution in 1 country.

Hai LiDepartment of Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Wei Chen
Yue Zhou
Parveen Abidi
Orr Sharpe
William H Robinson
Fredric B Kraemer
Jingwen Liu
VA Palo Alto Health Care System · US

Funding

Regulation of Liver LDL Receptor Expression by BerberineR01AT002543 · NCCIH · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI LIU, JINGWEN · 2005 to 2009
$1.7M
Statin-Berberine Combination Therapy in HyperlipidemiaR21AT003195 · NCCIH · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI LIU, JINGWEN · 2008 to 2009
$385k
NCCIH NIH HHS 1R01AT002543-01A1NCCIH NIH HHS 1R21 AT003195-01A2
6 · The paper itself

Abstract

The 3'untranslated region (UTR) of human LDL receptor (LDLR) mRNA contains three AU-rich elements (AREs) responsible for rapid mRNA turnover and mediates the stabilization induced by berberine (BBR). However, the identities of the specific RNA binding proteins involved in the regulation of LDLR mRNA stability at the steady state level or upon BBR treatment are unknown. By conducting small interfering RNA library screenings, biotinylated RNA pull-down, mass spectrometry analysis, and functional assays, we now identify heterogeneous nuclear ribonucleoprotein D (hnRNP D), hnRNP I, and KH-type splicing regulatory protein (KSRP) as key modulators of LDLR mRNA stability in liver cells. We show that hnRNP D, I, and KSRP interact with AREs of the LDLR 3'UTR with sequence specificity. Silencing the expression of these proteins increased LDLR mRNA and protein levels. We further demonstrate that BBR-induced mRNA stabilization involves hnRNP I and KSRP, as their cellular depletions abolished the BBR effect and BBR treatment reduced the binding of hnRNP I and KSRP to the LDLR mRNA 3'UTR. These new findings demonstrate that LDLR mRNA stability is controlled by a group of ARE binding proteins, including hnRNP D, hnRNP I, and KSRP. Our results suggest that interference with the ability of destabilizing ARE binding proteins to interact with LDLR-ARE motifs is likely a mechanism for regulating LDLR expression by compounds such as BBR and perhaps others.

Indexed as

Base SequenceRNA Stability3' Untranslated RegionsBerberineCell LineGenes, ReporterHeterogeneous-Nuclear Ribonucleoprotein DHeterogeneous-Nuclear RibonucleoproteinsHumansMolecular Sequence DataPolypyrimidine Tract-Binding ProteinReceptors, LDLRNA-Binding ProteinsRNA, MessengerRNA, Small InterferingTrans-Activators3' Untranslated RegionsBerberineHeterogeneous-Nuclear Ribonucleoprotein DHeterogeneous-Nuclear RibonucleoproteinsKHSRP protein, humanPolypyrimidine Tract-Binding ProteinPTBP1 protein, humanReceptors, LDLRNA-Binding ProteinsRNA, MessengerRNA, Small InterferingTrans-Activators

Identifiers

PMID19141871
PMCPMC2666168
OpenAlexW2170397176

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.