Evidence map›Paper›PMID 24393468›Full record

ArticleGenome biology2014

Advancing the functional utility of PAR-CLIP by quantifying background binding to mRNAs and lncRNAs.

Matthew B Friedersdorf, Jack D Keene

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 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
7.9field-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

80 citing papers in PubMed, 124 citations in OpenAlex.

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  20. TET2 chemically modifies tRNAs and regulates tRNA fragment levels.Nature structural & molecular biology · 2021
    Article

20 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

2 authors at 1 institution in 1 country.

Matthew B Friedersdorf
Jack D Keene
Duke University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
RNA Dynamics of Transient Macromolecular Complexes in Cancer CellsR01CA157268 · NCI · DUKE UNIVERSITY · PI KEENE, JACK D · 2011 to 2015
$1.7M
NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA157268NCI NIH HHS R01CA157268
6 · The paper itself

Abstract

backgroundSequence specific RNA binding proteins are important regulators of gene expression. Several related crosslinking-based, high-throughput sequencing methods, including PAR-CLIP, have recently been developed to determine direct binding sites of global protein-RNA interactions. However, no studies have quantitatively addressed the contribution of background binding to datasets produced by these methods.

resultsWe measured non-specific RNA background in PAR-CLIP data, demonstrating that covalently crosslinked background binding is common, reproducible and apparently universal among laboratories. We show that quantitative determination of background is essential for identifying targets of most RNA-binding proteins and can substantially improve motif analysis. We also demonstrate that by applying background correction to an RNA binding protein of unknown binding specificity, Caprin1, we can identify a previously unrecognized RNA recognition element not otherwise apparent in a PAR-CLIP study.

conclusionsEmpirical background measurements of global RNA-protein crosslinking are a necessary addendum to other experimental controls, such as performing replicates, because covalently crosslinked background signals are reproducible and otherwise unavoidable. Recognizing and quantifying the contribution of background extends the utility of PAR-CLIP and can improve mechanistic understanding of protein-RNA specificity, protein-RNA affinity and protein-RNA association dynamics.

Indexed as

Binding SitesChromosome MappingHEK293 CellsHigh-Throughput Nucleotide SequencingHumansRNA-Binding ProteinsRNA, Long NoncodingRNA, MessengerSequence Analysis, RNARNA-Binding ProteinsRNA, Long NoncodingRNA, Messenger

Identifiers

PMID24393468
PMCPMC4053780
OpenAlexW2118994852

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.